Systems and methods of de-endothelialization

FIELD OF THE INVENTION

The field of the invention pertains to embolizing blood vessels or aneurysms, and more particularly, to systems and methods for reducing blood vessel or aneurysm recanalization.

BACKGROUND

In many clinical situations, blood vessels are occluded for a variety of purposes, such as to control bleeding, to prevent blood supply to tumors, to stop blood flow to arterio-venous malformations or fistulas, and to block blood flow within an aneurysm.

Embolization of blood vessels is particularly useful in treating aneurysms. Aneurysms are abnormal blood-filled dilations of a blood vessel wall that may rupture causing significant bleeding. For the cases of intracranial aneurysms, the significant bleeding may lead to damage to surrounding brain tissue or death. Intracranial aneurysms may be difficult to treat when they are formed in remote cerebral blood vessels, which are very difficult to access. If left untreated, hemodynamic forces of normal pulsatile blood flow can rupture fragile tissue in the area of the aneurysm causing a stroke.

Vaso-occlusive devices have been used to treat aneurysms. Vaso-occlusive devices are surgical implants placed within blood vessels or vascular cavities, typically using a catheter, to form a thrombus and occlude the site. For instance, a stroke or other such vascular accident may be treated by placing a vaso-occlusive device proximal of the site to block the flow of blood to the site and alleviate the leakage. An aneurysm may similarly be treated by introducing a vaso-occlusive device through the neck of the aneurysm. The thrombogenic properties of the vaso-occlusive device cause a mass to form in the aneurysm and alleviate the potential for growth of the aneurysm and its subsequent rupture. Other diseases, such as tumors, may often be treated by occluding the blood flow to the tumor.

There are a variety of vaso-occlusive devices suitable for forming thrombi. One such device is found in U.S. Pat. No. 4,994,069, to Ritchart et al., the entirety of which is expressly incorporated by reference herein. That patent describes a vaso-occlusive coil that assumes a linear helical configuration when stretched and a folded convoluted configuration when relaxed. The stretched configuration is used to deliver the coil to the desired site and the convoluted configuration occurs when the coil is ejected from the catheter and the coil relaxes. Ritchart et al. describes a variety of shapes, including “flower” shapes and double vortices. A random shape is described as well.

U.S. Pat. No. 6,280,457B1 to Wallace et al., describes an occlusive device comprising an inner core wire covered with a polymer. The polymeric material includes protein based polymers, absorbable polymers, non-protein based polymers, and combinations thereof. The polymer may contribute to forming emboli for occluding a body cavity.

Vaso-occlusive coils having complex, three-dimensional structures in a relaxed configuration are described in U.S. Pat. No. 6,322,576B1 to Wallace et al. The coils may be deployed in the approximate shape of a sphere, an ovoid, a clover, a box-like structure or other distorted spherical shape. The patent also describes methods of winding the anatomically shaped vaso-occlusive device into appropriately shaped forms and annealing them to form various devices.

Vaso-occlusive coils having little or no inherent secondary shape have also been described. For instance, co-owned U.S. Pat. Nos. 5,690,666 and 5,826,587 by Berenstein et al., describe coils having little or no shape after introduction into the vascular space.

Vaso-occlusive devices work initially by slowing blood flow inside the aneurysm. As a result of the slowed blood flow, the blood inside the aneurysm clots. The combination of the vaso-occlusive devices and the clot protects the aneurysm from hemodynamic forces (i.e., forces on the aneurysm wall due to blood flow) that may cause recanalization and recurrence of the aneurysm. However, recanalization and recurrence of the aneurysm may still occur for various reasons. For example, the vaso-occlusive device may rearrange itself due to the hemodynamic forces. Typically, the vaso-occlusive device(s) near the neck of the aneurysm is most affected by the effects of blood flow. Also, the clot formed may break down due to the hemodynamic forces and/or natural chemical processes. This is more likely to occur if the aneurysm is loosely packed with vaso-occlusive devices.

Accordingly, devices and methods for reducing recanalization or recurrence of an aneurysm would be useful.

SUMMARY OF THE INVENTION

The present invention is directed to apparatus and methods for treating aneurysms or other body cavities. More particularly, the present invention is directed to apparatus and methods for disrupting the endothelium of the wall of an aneurysm to reduce the risk of the wall expanding, thinning, and/or or rupturing, or to reduce the risk of recanalization of a body cavity, such as an arterio-venous malformation, fistula, or other blood vessel.

In accordance with one aspect of the present invention, an apparatus for disrupting an endothelium of an aneurysm or other body lumen wall is provided. Generally, the apparatus includes an elongate member including a proximal end and a distal end configured for insertion into a body lumen of a patient. The distal end of the elongate member may have a primary shape, e.g., a substantially linear relaxed shape, a curvilinear relaxed shape, and/or a helical coil shape. Optionally, the elongate member may have a secondary shape, e.g., a three-dimensional shape towards which the elongate member may be biased in a relaxed state free from external forces. The elongate member may be formed from an elastic or superelastic material and/or a bioabsorbable material.

Any of the apparatus described herein may include a delivery device, e.g., a sheath, catheter or other tubular member, for delivering the elongate member. For example, the distal end of the elongate member may be disposed within a lumen of the tubular member as a distal end of the tubular member is advanced to a treatment site, e.g., to prevent the distal end from contacting tissue prematurely, i.e., until deployed.

Optionally, the distal end of the elongate member may be deployable such that the distal end may remain within the aneurysm or other body cavity upon completing the procedure. The distal end of the elongate member may be deployable using a mechanical joint, an electrolytic joint, and/or a dissolvable adhesive. In addition or alternatively, the distal end of the elongate member may be steerable, e.g., to guide the distal end around bends, into a body cavity, such as an aneurysm sac, and/or otherwise manipulating the distal end during a procedure.

In one embodiment, one or more abrasive elements are carried on the distal end of the elongate member for disrupting the endothelium of the aneurysm or other body cavity. The abrasive element(s) may include hooks, needles, fins, saw tooth elements, and/or sharp particles. The abrasive element(s) that may be disposed on an entire exposed surface of the distal end of the elongate member or may be selectively disposed in a pattern on only a portion of the distal end. Preferably, the abrasive element(s) has(have) a size and stiffness for disrupting the endothelium of a vessel wall, e.g., a wall of an aneurysm, without substantial risk of penetrating completely through the wall.

Optionally, an expandable member may be carried by the distal end of the elongate member, the abrasive elements being carried on the expandable member. For example, the expandable member may be an expandable basket including one or more splines, each carrying one or more abrasive elements. Alternatively, the expandable member may be an elastic or inelastic balloon that may be expanded upon introducing fluid into an interior of the balloon. If the elongate member includes an expandable member, the expandable member may be collapsed when disposed within a delivery device, e.g., a sheath or other tubular member. The expandable member may be biased to expand towards an expanded configuration when deployed from the delivery device or may be controllably expanded, e.g., mechanically or using a fluid. In addition, the balloon may be porous and/or may include one or more openings or lumens for delivering a fluid, e.g., a de-endothelialization fluid beyond an outer surface of the balloon, as explained further below.

An apparatus, such as those described above, may be used for de-endothelializing an aneurysm. Initially, an apparatus may be provided that includes an elongate member carrying one or more abrasive elements on its distal end. The distal end may be introduced into a body lumen, e.g., a patient's vasculature, and advanced until the distal end reaches a target site intended for treatment, e.g., an aneurysm within a cerebral or other artery. The distal end may be provided within a catheter or other delivery device to protect the vasculature from being damaged by the abrasive elements and/or to protect the distal end of the elongate member.

For example, a delivery catheter may be positioned adjacent an aneurysm, and the distal end of the elongate member may be advanced from a lumen of the catheter into the aneurysm. The distal end of the elongate member may be manipulated, e.g., advanced, retracted, steered, and/or rotated to engage the abrasive elements with the wall of the aneurysm to disrupt the endothelium of the wall. If an expandable member is carried on the distal end, the expandable member may be expanded to enhance engaging the endothelium with the abrasive elements. Consequently, the patient's body may react to the disruption by generating fibrous tissue, e.g., scar tissue, that may thicken or otherwise strengthen the wall of the aneurysm, thereby substantially reducing the risk of the wall thinning further and/or the aneurysm growing or rupturing.

The elongate member may then be retracted into the catheter and both removed from the patient. Alternatively, the distal end of the elongate member may be released from the elongate member to at least partially fill the aneurysm.

In accordance with another aspect of the present invention, another apparatus for disrupting an endothelium of an aneurysm or other body cavity wall is provided that uses thermal energy to disrupt the endothelium. Similar to the previous embodiments, the apparatus may include an elongate member having a distal end, which may be steerable and/or deployable, as described above. A thermal element may be carried by the distal end of the elongate member that is configured for being heated or cooled to a de-endothelializing temperature. Similar to the previous embodiment, the distal end may include an expandable member, e.g., an expandable basket or balloon, that may carry the heating or cooling element.

In one form, the thermal element may be an electrically resistive heating element that may be coupled to a source of electrical energy. Upon delivering electrical energy to the distal end, the resistive heating element may become heated sufficiently to disrupt the endothelium that it contacts directly or that is heated by conduction and/or convection. Alternatively, the thermal element may be an energy storage element that may be heated or cooled before being inserted through a thermally insulated delivery device, e.g., a sheath, that has been placed adjacent the aneurysm.

In a further alternative, the thermal element may be an expandable balloon or other hollow element. The hollow element may be filled with a heated or cooled fluid to heat or cool the hollow element to a desired temperature for de-endothelializing the wall of an aneurysm that it contacts directly or to which it is coupled by conduction or convection. Optionally, the hollow element may include one or more openings such that the heated or cooled fluid may be delivered from the hollow element into the aneurysm or body cavity to disrupt the endothelium of the wall. In this embodiment, the elongate member and/or the delivery device may include a sealing member that may be used to at least partially seal the aneurysm or a body lumen communicating with the aneurysm.

These embodiments may be used to disrupt the endothelium of an aneurysm or other body cavity wall using thermal energy. The distal end of the elongate member may be advanced from a delivery device, such as a sheath or catheter, into the aneurysm. For example, the delivery device may be advanced through the patient's vasculature with the elongate member therein. Once the delivery device is adjacent to the aneurysm, the distal end of the elongate member may be advanced from the delivery device to place the thermal element within the aneurysm.

If the thermal element includes an electrically resistive heating element, electrical energy may be delivered to the heating element, thereby heating the interior of the aneurysm and/or heating the wall contacted by the heating element until the endothelium is disrupted. Alternatively, if the thermal element includes an expandable member, the expandable member may be expanded within the aneurysm to at least partially fill the aneurysm cavity.

In addition or alternatively, if the thermal element is porous or includes outlet ports coupled to a source of heated or cooled fluid via a lumen, the fluid may be delivered into the aneurysm to disrupt the endothelium. Optionally, a sealing member may be located proximal to the thermal element that may be expanded or otherwise engaged with the neck of the aneurysm to substantially seal the aneurysm. This may prevent fluid delivered into the aneurysm from escaping into adjacent body lumen(s). Preferably, the fluid is heated to a temperature above fifty degrees Celsius (50° C.) or cooled to a temperature below zero degrees Celsius (0° C.).

In accordance with yet another aspect of the present invention, a method is provided for treating a wall of an aneurysm, arterio-venous malformation, fistula, or other a body lumen. A tubular member may be introduced into the vasculature until a distal end of the tubular member is located within the aneurysm or blood vessel. A fluid may be delivered via a lumen of the tubular member into the aneurysm or blood vessel to at least partially de-endothelialize the wall of the aneurysm or blood vessel. This may cause an endothelium of the wall to generate fibrous tissue to strengthen the wall of the aneurysm or to strengthen and/or occlude the blood vessel.

In one embodiment, a sealing member may be carried by one of the inner and outer members, and the sealing member may be engaged with a neck of the aneurysm to substantially sealing the aneurysm before the fluid is delivered into the aneurysm. In an exemplary embodiment, the sealing member may include an annular shaped member including an outer wall and a passage extending therethrough, and wherein the annular shaped member positioned such that the outer wall is disposed adjacent the neck of the aneurysm to substantially seal the aneurysm and the passage is disposed coaxially within the body lumen to allow continued fluid flow along the body lumen.

In addition or alternatively, the tubular member may include a balloon carried on the distal end thereof, and wherein the fluid is delivered via the balloon. For example, the balloon may include one or more openings extending through a wall of the balloon and communicating with an interior of the balloon, the fluid being delivered into the aneurysm through the one or more openings. In one embodiment, the fluid may be introduced into the interior of the balloon, thereby expanding the balloon until the one or more openings expand sufficiently to allow the fluid to exit from the interior of the balloon through the one or more openings. Alternatively, the balloon may include a delivery lumen formed within a wall of the balloon and the fluid may be delivered into the aneurysm through the delivery lumen. In another alternative, the balloon may carry one or more abrasive elements configured for disrupting the endothelium of the wall of the aneurysm, as described above.

In accordance with yet another aspect of the present invention, a method is provided for treating a wall of an aneurysm, blood vessel, or other body lumen. A tubular member may be introduced into the body lumen until a distal end of the tubular member is located adjacent the aneurysm, the distal end carrying an annular shaped member. The annular shaped member may be expanded until an outer wall of the annular shaped member engages a neck of the aneurysm to substantially seal the aneurysm, the annular shaped member including a passage extending-therethrough to allow continued fluid flow along the body lumen. A fluid may be delivered into the aneurysm to at least partially de-endothelialize the wall of the aneurysm, thereby causing an endothelium of the wall to generate fibrous tissue to strengthen the wall of the aneurysm.

In accordance with still another aspect of the present invention, an apparatus is provided for disrupting an endothelium of an aneurysm or other body lumen that includes an outer member including a proximal end and a distal end having a size and shape for insertion into a body lumen communicating with an aneurysm or other body lumen. An inner member may be deployable from within the outer member that includes a proximal end, a distal end having a size and shape for insertion into an aneurysm cavity or body lumen, and a lumen extending between the proximal end and an outlet port on the distal end. A source of de-endothelialization fluid may be coupled to the proximal end of the tubular member and communicating with the first lumen. A sealing member may be carried by one of the inner and outer members proximal to the outlet port, the sealing member having a size and shape for substantially sealing a neck of the aneurysm or other body lumen.

In accordance with yet another aspect of the present invention, a method is provided for treating a malformation extending from a body lumen, such as an arterio-venous malformation or fistula. A tubular member may be introduced into the body lumen until a distal end of the tubular member is located within the malformation. The malformation may be substantially sealed from the body lumen, and fluid aspirated from within the malformation. For example, the malformation may be flushed with fluid, such as saline, and excess fluid may be aspirated from the malformation to substantially clear the malformation. Preferably, the malformation is flushed and aspirated substantially simultaneously.

In one embodiment, the malformation may be substantially sealed form the body lumen by expanding an occlusion member carried on the distal end of the tubular member to engage an entrance into the malformation. In another embodiment, an occlusion member, such as a compliant balloon, may be introduced into the body lumen until the occlusion member is adjacent the malformation and then expanded to engage an entrance to the malformation.

A therapeutic fluid may be delivered via the tubular member into the malformation, e.g., to at least partially de-endothelialize an endothelium of the malformation. In addition or alternatively, the therapeutic fluid may cause at least one of the following to occur within the malformation: cellular lysis, disruption of cellular or intercellular adhesions, and disruption of cellular function. Thereafter, the therapeutic fluid may be aspirated from the malformation, e.g., by simultaneous flushing and aspirating. If one or more occlusion members were used to seal malformation, the occlusion member(s) may be collapsed or otherwise removed from the body lumen, allowing the malformation to communicate with the body lumen.

Where the malformation is an arterio-venous malformation or fistula, e.g., extending between an artery and a vein or two other blood vessels, an occlusion may be introduced into the artery or first vessel to substantially isolate the artery or first vessel from the arterio-venous malformation. Another occlusion member may be introduced into the vein or second vessel to substantially isolate the vein or second vessel from the arterio-venous malformation. Thus, the malformation may be substantially isolated from both vessels, e.g., to allow flushing, aspiration, and/or therapeutic fluid infusion only within the malformation. Where infusion and aspiration are simultaneous, one of the occlusion members may be used for infusion, while the other occlusion member may be used for aspiration.

In accordance with still another aspect of the present invention, an apparatus is provided for disrupting an endothelium of a wall of an aneurysm or other body lumen that includes an elongate core member having an outer surface, a proximal end, and a distal end having a size and shape for introduction into an aneurysm or other body lumen. One or more fibers are provided on the outer surface of the core member, the one or more fibers carrying a de-endothelialization agent.

The apparatus may be used to at least partially de-endothelialize a wall of an aneurysm or other body lumen. The core member may be introduced into the aneurysm or other body lumen, thereby releasing the fluid from the one or more fibers within the aneurysm or other body lumen, the fluid disrupting at least a portion of the endothelium of the wall of the, aneurysm or other body lumen. The core member may be dipped in a source of de-endothelialization fluid such that the one or more fibers absorb the fluid.

Alternatively, the core member may include a coating, e.g., a hydrogel, on the outer surface of the core member that is degradable when exposed to bodily fluid, the coating including a de-endothelialization agent that is released as the degrades.

To at least partially de-endothelialize a wall of an aneurysm or other body lumen, the core member may be introduced into the aneurysm. The core member may be left within the aneurysm or other body lumen until the coating at least degrades to release the de-endothelialization agent within the aneurysm or other body lumen, whereby the agent may at least partially de-endothelialize a wall of the aneurysm or other body lumen.

Other objects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate the design and utility of preferred embodiments of the present invention, in which similar elements are referred to by common reference numerals. In order to better appreciate how the advantages and objects of the present inventions are obtained, a more particular description of the present inventions briefly described above will be rendered by reference to specific embodiments thereof, which are illustrated in the accompanying drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings.

<figref idrefs="DRAWINGS">FIG. 1</figref> is a side view of a de-endothelialization device.

<figref idrefs="DRAWINGS">FIG. 2A-2F</figref> are details of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 1</figref>, showing various embodiments of an abrasive element.

<figref idrefs="DRAWINGS">FIGS. 3-11</figref> are exemplary secondary shapes of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 1</figref>.

<figref idrefs="DRAWINGS">FIG. 12</figref> is a partial cross-sectional side view of a catheter for delivering a de-endothelialization device into an aneurysm.

<figref idrefs="DRAWINGS">FIG. 13</figref> is a partial cross-sectional side view of a catheter delivering a de-endothelialization device therefrom.

<figref idrefs="DRAWINGS">FIG. 14</figref> is a partial cross-sectional side view of a catheter delivering another de-endothelialization device therefrom.

<figref idrefs="DRAWINGS">FIG. 15</figref> is a partial cross-sectional side view of a catheter delivering yet another de-endothelialization device therefrom, showing the de-endothelialization device adopting a secondary shape as it is deployed.

<figref idrefs="DRAWINGS">FIG. 16</figref> is a partial cross-sectional detail of a de-endothelialization device coupled to a core wire by a mechanical joint.

<figref idrefs="DRAWINGS">FIG. 17</figref> is a partial cross-sectional detail of a de-endothelialization device coupled to a core wire by an electrolytic link.

<figref idrefs="DRAWINGS">FIG. 18</figref> is a partial cross-sectional side view of a de-endothelialization device coupled to a core member and being deployed from a delivery catheter.

<figref idrefs="DRAWINGS">FIG. 19</figref> is a partial cross-sectional side view of an alternative embodiment of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 18</figref>, showing the de-endothelialization device having a curvilinear relaxed shape.

<figref idrefs="DRAWINGS">FIG. 20</figref> is a partial cross-sectional side view of another alternative embodiment of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 18</figref>, showing the de-endothelialization device having a relaxed shape of a spiral.

<figref idrefs="DRAWINGS">FIG. 21A</figref> is a top view of an embodiment of a de-endothelialization device including a steering mechanism.

<figref idrefs="DRAWINGS">FIG. 21B</figref> is a partial cross-sectional top view of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 21A</figref> expanded after being deployed from the catheter.

<figref idrefs="DRAWINGS">FIG. 22A</figref> is a side view of a de-endothelialization device including a basket and being deployed from a delivery catheter.

<figref idrefs="DRAWINGS">FIG. 22B</figref> is a partial side view of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 22A</figref> expanded after being deployed from the catheter.

<figref idrefs="DRAWINGS">FIG. 23</figref> is a detail of a variation of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 22A</figref>, showing the basket rotatably coupled to a core wire.

<figref idrefs="DRAWINGS">FIG. 24</figref> is a side view of an alternative embodiment of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 22A</figref>, showing a distal end of the core wire biased to define an angle with an axis of a proximal portion of the core wire.

<figref idrefs="DRAWINGS">FIG. 25A</figref> is a partial cross-sectional side view of a de-endothelialization device including a balloon and coupled to a core wire.

<figref idrefs="DRAWINGS">FIG. 25B</figref> is a partial cross-sectional side view of a variation of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 25A</figref>, showing abrasive elements forming a pattern at the distal end of the balloon.

<figref idrefs="DRAWINGS">FIG. 26</figref> is a side view of a de-endothelialization device.

<figref idrefs="DRAWINGS">FIGS. 27 and 28</figref> are partial cross-sectional side views of a de-endothelialization delivery device, including a de-endothelialization device having a helical coil shape when disposed and deployed from the delivery device.

<figref idrefs="DRAWINGS">FIG. 29A</figref> is a partial cross-sectional side view of a de-endothelialization device electrically coupled to a generator.

<figref idrefs="DRAWINGS">FIG. 29B</figref> is a partial cross-sectional side view of a de-endothelialization device conductively coupled to a heatable element.

<figref idrefs="DRAWINGS">FIG. 30</figref> is a cross-sectional side view of a de-endothelialization device including an operative element for delivering heat to an endothelium of an aneurysm.

<figref idrefs="DRAWINGS">FIG. 31</figref> is a cross-sectional view of a de-endothelialization fluid delivery device delivering fluid into an aneurysm.

<figref idrefs="DRAWINGS">FIG. 32</figref> is a cross-sectional detail of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 31</figref>.

<figref idrefs="DRAWINGS">FIG. 33A</figref> is a cross-sectional detail of another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 31</figref> including a drainage port.

<figref idrefs="DRAWINGS">FIG. 33B</figref> is a cross-sectional detail of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 33A</figref>.

<figref idrefs="DRAWINGS">FIG. 33C</figref> is a cross-sectional detail of another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 33A</figref>.

<figref idrefs="DRAWINGS">FIG. 33D</figref> is a cross-sectional detail of yet another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 33A</figref> including an inner tube.

<figref idrefs="DRAWINGS">FIG. 34A</figref> is a cross-sectional detail of another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 32</figref> including a stopper.

<figref idrefs="DRAWINGS">FIG. 34B</figref> is a detail of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 34A</figref>, showing the stopper in a low profile disposed within a sheath.

<figref idrefs="DRAWINGS">FIG. 34C</figref> is a detail of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 34A</figref> including a stopper.

<figref idrefs="DRAWINGS">FIG. 34D</figref> is a detail of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 34C</figref>, showing the stopper compressed into a low profile within a sheath.

<figref idrefs="DRAWINGS">FIG. 34E</figref> is a partial cross-sectional side view of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 34A</figref>, showing the stopper being deployed within an aneurysm.

<figref idrefs="DRAWINGS">FIG. 34F</figref> is a cross-sectional side view of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 34A</figref>, showing a stopper having an elliptical shape.

<figref idrefs="DRAWINGS">FIG. 35</figref> is a partial cross-sectional side view of an alternative embodiment of a de-endothelialization fluid delivery device.

<figref idrefs="DRAWINGS">FIG. 36</figref> is a partial cross-sectional side view of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 35</figref>.

<figref idrefs="DRAWINGS">FIG. 37</figref> is a partial cross-sectional side view of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 36</figref>.

<figref idrefs="DRAWINGS">FIG. 38A</figref> is a partial side view of a de-endothelialization fluid delivery device including a balloon deployed within an aneurysm.

<figref idrefs="DRAWINGS">FIG. 38B</figref> is a cross section of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 38A</figref>.

<figref idrefs="DRAWINGS">FIG. 39A</figref> is a cross-sectional view of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 38A</figref> including a balloon having a drainage port.

<figref idrefs="DRAWINGS">FIG. 39B</figref> is a cross sectional view of the delivery tube of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 39A</figref> taken along line <b>39</b>B-<b>39</b>B.

<figref idrefs="DRAWINGS">FIG. 40A</figref> is a cross section of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 39A</figref> including a drainage port coupled to a drainage tube.

<figref idrefs="DRAWINGS">FIG. 40B</figref> is a cross sectional view of the delivery tube of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 40A</figref> taken along line <b>40</b>B-<b>40</b>B.

<figref idrefs="DRAWINGS">FIG. 41</figref> is a cross-sectional view of a variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 38A</figref> including a stopper.

<figref idrefs="DRAWINGS">FIG. 42</figref> is a side view of a de-endothelialization fluid delivery device including a triple-lumen catheter.

<figref idrefs="DRAWINGS">FIG. 42A</figref> is a cross-sectional view of another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 38A</figref>, including a fluid delivery lumen formed within a wall of the balloon for delivering de-endothelialization fluid.

<figref idrefs="DRAWINGS">FIG. 42B</figref> is a cross-sectional view of another variation of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 38A</figref> including a separate tube coaxially surrounded by the delivery tube.

<figref idrefs="DRAWINGS">FIG. 43A</figref> is a side view of a de-endothelialization system including a perfusion balloon.

<figref idrefs="DRAWINGS">FIG. 43B</figref> is a perspective view of a variation of the perfusion balloon of the de-endothelialization system of <figref idrefs="DRAWINGS">FIG. 43A</figref>.

<figref idrefs="DRAWINGS">FIG. 43C</figref> is a cross sectional view of the perfusion balloon of <figref idrefs="DRAWINGS">FIG. 43B</figref> taken along line <b>43</b>C-<b>43</b>C.

<figref idrefs="DRAWINGS">FIG. 44A</figref> is a side view of a de-endothelialization fluid delivery device including a triple-lumen catheter.

<figref idrefs="DRAWINGS">FIG. 44B</figref> is a cross sectional view of the triple-lumen catheter of <figref idrefs="DRAWINGS">FIG. 44A</figref> taken along line <b>44</b>B-<b>44</b>B.

<figref idrefs="DRAWINGS">FIG. 44C</figref> is a cross-sectional view of a variation of the triple-lumen catheter of <figref idrefs="DRAWINGS">FIG. 44A</figref>.

<figref idrefs="DRAWINGS">FIG. 44D</figref> is a cross-sectional view of another variation of the triple-lumen catheter of <figref idrefs="DRAWINGS">FIG. 44A</figref>.

<figref idrefs="DRAWINGS">FIG. 45</figref> is a side view of a de-endothelialization fluid delivery device including an expandable applicator deployable from a delivery sheath.

<figref idrefs="DRAWINGS">FIG. 46</figref> is a partial cross-sectional view of the de-endothelialization fluid delivery device of <figref idrefs="DRAWINGS">FIG. 45</figref>, showing the applicator compressed into a low profile within the sheath.

<figref idrefs="DRAWINGS">FIG. 47</figref> is a side view of a de-endothelialization device including a fiber attached to an elongate core member.

<figref idrefs="DRAWINGS">FIG. 48</figref> is a side view of a variation of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 47</figref>.

<figref idrefs="DRAWINGS">FIG. 49</figref> is a side view of another variation of the de-endothelialization device of <figref idrefs="DRAWINGS">FIG. 47</figref>.

<figref idrefs="DRAWINGS">FIG. 50</figref> is a cross-sectional side view of a de-endothelialization device including a coating containing a de-endothelializing compound therein.

<figref idrefs="DRAWINGS">FIG. 51</figref> is a cross-sectional side view of a de-endothelialization device including a hydrogel coating on an elongate core member.

<figref idrefs="DRAWINGS">FIGS. 52A-52E</figref> show a blood vessel with an aneurysm being treated using a dual catheter system, in accordance with the present invention.

<figref idrefs="DRAWINGS">FIG. 53</figref> is a cross-sectional side view of a dual syringe system for simultaneously injecting and aspirating fluid, in accordance with the present invention.

<figref idrefs="DRAWINGS">FIG. 54</figref> shows an arterio-venous malformation being treated using a dual catheter system, in accordance with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Systems and methods of de-endothelializing an aneurysm or other body lumen are described herein. As used in this specification, “de-endothelializing” or “de-endothelialization” refers to the process of disrupting an endothelium of an aneurysm or other body lumen, which includes removing, damaging physically, damaging normal biochemical function, or otherwise damaging and/or destroying a part or all of the endothelium of the wall of an aneurysm or other body lumen. The first part of the specification discusses systems and methods of de-endothelializing an aneurysm or other body lumen using mechanical instrumentality. The second part of the specification discusses systems and methods of de-endothelializing an aneurysm or other body lumen using a thermal treatment. The third part of the specification discusses systems and methods of de-endothelializing an aneurysm or other body lumen using a fluid.

I. De-Endothelialization Using Mechanical Instrumentality

A. Implantable De-Endothelialization Devices

<figref idrefs="DRAWINGS">FIGS. 1-11</figref> show variations of a de-endothelialization device <b>10</b>. The de-endothelialization device <b>10</b> includes a core member <b>12</b> and one or more abrasive elements <b>14</b> coupled to the core member <b>12</b>. In general, the core member <b>12</b> carries the abrasive element(s) <b>14</b>, which are adapted for disrupting an endothelium of an aneurysm. Optionally, the de-endothelialization device <b>10</b>(<b>1</b>) may include an end cap <b>18</b>, as shown in <figref idrefs="DRAWINGS">FIG. 1</figref>, e.g., a rounded and/or substantially blunt distal tip.

<figref idrefs="DRAWINGS">FIG. 1</figref> shows a de-endothelialization device <b>10</b>(<b>1</b>) that has an elongate core member <b>12</b>(<b>1</b>) adapted to be implanted within an aneurysm. The core member <b>12</b>(<b>1</b>) preferably has a circular cross-sectional shape. Alternatively, the core member <b>12</b>(<b>1</b>) may have a rectangular, a triangular, or other geometric cross-sections. The core member <b>12</b>(<b>1</b>) may even have an irregular shaped cross-section.

The core member <b>12</b>(<b>1</b>) is preferably made of biodegradable materials. Biodegradable or absorbable materials suitable for use in the compositions of the core member <b>12</b>(<b>1</b>) may include polymers and proteins. Suitable polymers include, for example, polyglycolic acid, polylactic acid, polycaprolactone, polyhydroxybutyrate, polyhydroxyvalerate, polydioxanone, polycarbonates, polyanhydrides, polyhydroxyalkanoates, polyarylates, polysaccharides, polyamino acids, and copolymers thereof. Non-limiting examples of bioabsorbable proteins include collagen, elastin, fibrinogen, fibronectin, vitronectin, laminin and gelatin. Many of these materials are commercially available. Fibrin-containing compositions are commercially available, for example, from Baxter. Collagen containing compositions are commercially available, for example, from Cohesion Technologies, Inc., Palo Alto, Calif. Fibrinogen-containing compositions are described, for example, in U.S. Pat. Nos. 6,168,788 and 5,290,552, the entirety of which is expressly incorporated by reference herein. As will be readily apparent, absorbable materials can be used alone or in any combination with each other. The absorbable material may be in the form of a mono-filament or, alternatively, multi-filament strands.

Furthermore, the absorbable materials may be used in combination with additional components. For example, lubricious materials (e.g., hydrophilic) materials may be used to coat the member. One or more bioactive materials may also be included in the composition of the core member <b>12</b>(<b>1</b>). The term “bioactive” refers to any agent that exhibits effects in vivo, for example, a thrombotic agent, a therapeutic agent, and the like. Examples of bioactive materials include cytokines; extra-cellular matrix molecules (e.g., collagen); trace metals (e.g., copper); matrix metalloproteinase inhibitors; and other molecules that stabilize thrombus formation or inhibit clot lysis (e.g., proteins or functional fragments of proteins, including but not limited to Factor XIII, α₂-antiplasmin, plasminogen activator inhibitor-1 (PAI-1) or the like). Examples of cytokines that may be used alone or in combination in practicing the present invention include basic fibroblast growth factor (bFGF), platelet derived growth factor (pDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and the like. Cytokines, extra-cellular matrix molecules, and thrombus stabilizing molecules are commercially available from several vendors such as Genzyme (Framingham, Mass.), Genentech (South San Francisco, Calif.), Amgen (Thousand Oaks, Calif.), R&amp;D Systems, and Immunex (Seattle, Wash.). Additionally, bioactive polypeptides can be synthesized recombinantly as the sequence of many of these molecules are also available, for example, from the GenBank database. Thus, it is intended that the invention include use of DNA or RNA encoding any of the bioactive molecules.

Furthermore, it is intended that molecules having similar biological activity as wild-type or purified cytokines, matrix metalloproteinase inhibitors, extra-cellular matrix molecules, thrombus-stabilizing proteins (e.g., recombinantly produced or mutants thereof), and nucleic acid encoding these molecules may also be used. The amount and concentration of the bioactive materials that may be included in the composition of the core member <b>12</b>(<b>1</b>) may vary, depending on the specific application, and can be readily determined by one skilled in the art. It will be understood that any combination of materials, concentration, or dosage can be used so long as it is not harmful to the subject.

For the compositions of the core member <b>12</b>(<b>1</b>), it may also be desirable to include one or more radiopaque materials for use in visualizing the vaso-occlusive members <b>12</b>(<b>1</b>) in situ. Thus, the vaso-occlusive members <b>12</b>(<b>1</b>) may be coated or mixed with radiopaque materials such as metals (e.g. tantalum, gold, tungsten or platinum), barium sulfate, bismuth oxide, bismuth subcarbonate, and the like.

Alternatively, the core member <b>12</b>(<b>1</b>) may be made of non-biodegradable materials, such as metals or alloys, for examples, that are in general more elastic than the biodegradable materials described previously. Suitable metals and alloys for the wire making up the coil include the Platinum Group metals, especially platinum, rhodium, palladium, rhenium, as well as tungsten, gold, silver, tantalum, and alloys of these metals. These metals have significant radiopacity and their alloys may be tailored to accomplish an appropriate blend of flexibility and stiffness. They are also largely biologically inert. Additional coating materials, such as polymer, or biodegradable materials as discussed previously, may be added to the surface of the core member <b>12</b>(<b>1</b>) to improve the lubricity, healing properties, or thrombogenic properties of the vaso-occlusive device.

The core member <b>12</b>(<b>1</b>) may also be of any of a wide variety of stainless steels if some sacrifice of radiopacity may be tolerated. Very desirable materials of construction, from a mechanical point of view, are materials that maintain their shape despite being subjected to high stress. Certain “super-elastic alloys” include nickel/titanium alloys, copper/zinc alloys, or nickel/aluminum alloys. Alloys that may be used are also described in U.S. Pat. Nos. 3,174,851, 3,351,463, and 3,753,700, the entirety of which is expressly incorporated by reference herein.

Titanium/nickel alloys known as “nitinol” may also be used in the core member <b>12</b>(<b>1</b>). These are super-elastic and very sturdy alloys that will tolerate significant flexing without deformation even when used as a very small diameter wire. If nitinol is used in the device, the diameter of the core member <b>12</b>(<b>1</b>) may be significantly smaller than that of a core member <b>12</b>(<b>1</b>) that uses the relatively more ductile platinum or platinum/tungsten alloy as the material of construction.

The core member <b>12</b>(<b>1</b>) may also be made of radiolucent fibers or polymers (or metallic threads coated with radiolucent or radiopaque fibers) such as Dacron (polyester), polyglycolic acid, polylactic acid, fluoropolymers (polytetrafluoroethylene), Nylon (polyamide), or even silk.

The abrasive element(s) <b>14</b> may have a sharp edge (such as that of a cutting wire or a knife) or a sharp point, for the purpose of cutting, abrading, and/or penetrating an endothelium of an aneurysm. <figref idrefs="DRAWINGS">FIG. 2</figref> shows several examples of the shape of the abrasive element(s) <b>14</b>. The abrasive element <b>14</b> can have a shape of a hook (<figref idrefs="DRAWINGS">FIG. 2A</figref>), a needle (<figref idrefs="DRAWINGS">FIG. 2B</figref>), a fin (<figref idrefs="DRAWINGS">FIG. 2C</figref>), a saw tooth (<figref idrefs="DRAWINGS">FIG. 2D</figref>), a multi-branch hook (<figref idrefs="DRAWINGS">FIG. 2E</figref>), or a ninety degree hook (<figref idrefs="DRAWINGS">FIG. 2F</figref>). The abrasive element(s) <b>14</b> can also include one or more sharp particles, such as diamond dust, that has no specific geometric shape. It should be noted that the abrasive element(s) <b>14</b> can also have a customized shape or other shapes as well. The abrasive element(s) <b>14</b> can have a wide range of stiffness, so long as the abrasive element(s) <b>14</b> is capable of disrupting an endothelium of an aneurysm. Furthermore, in order to prevent over-thinning of the arterial or aneurysm wall, that can risk punctures of the arterial or aneurysm wall, the abrasive element (s) <b>14</b> may have an overall depth that is less than about five microns. Depending on the particular application, the abrasive element(s) <b>14</b> may also have an overall depth that is more than about five microns.

As a further alternative, the abrasive element <b>14</b> may be an abrasive fibrous structure having fibers adapted for disrupting an endothelium of an aneurysm. The fibrous structure is preferably coupled to the core member <b>12</b> by frictional contact between the fibrous structure and the outer surface of the core member <b>12</b>. The surface of the core member <b>12</b> may be textured to improve coupling between the fibrous structure and the core member <b>12</b>. The core member <b>12</b> may also include one or more transverse openings along the length of the core member <b>12</b>, through which strands of the fibrous structure can be wrapped to secure the fibrous structure to the core member <b>12</b>. Alternatively, the core member <b>12</b> may also include protrusions along the length of the core member <b>12</b>, around which strands of the fibrous structure can be wrapped or hooked to secure the fibrous structure to the core member <b>12</b>. Alternatively, an adhesive, such as ultraviolet-curable adhesives, silicones, cyanoacrylates, and epoxies, may be used to secure the fibrous structure to the core member <b>12</b>. Furthermore, the fibrous structure may be coupled to the core member <b>12</b> by chemical bonding between reactive groups on the fibrous structure and the core member <b>12</b>, fusing both materials so that they melt together, or temporarily melting the surface of the core member <b>12</b> to embed strands of the fibrous structure.

The abrasive element <b>14</b> can be made from a variety of materials, such as polymers, metals, or plastics. Any of the materials discussed previously in reference to the core member <b>12</b> may also be suitable for the abrasive element <b>14</b>. The abrasive element <b>14</b> can be coupled to the core member <b>12</b> by a polymer, glue, weld, or brazing. Other types of adhesive may also be used, depending on the materials from which the abrasive element <b>14</b> and the core member <b>12</b> are made. Alternatively, the abrasive element <b>14</b> and the core member <b>12</b> can be fabricated together as a single unit during a manufacturing process. For example, the abrasive element <b>14</b> can be created by removing part(s) of the surface of the core member <b>12</b>. The abrasive element <b>14</b> may also be molded together with the core member <b>12</b> when the de-endothelialization device <b>10</b> is manufactured. It should be noted that the number of abrasive elements <b>14</b>, and the patterns or configurations formed by the abrasive elements <b>14</b>, on the surface of the core member <b>12</b> may vary. For example, the de-endothelialization device <b>10</b> can have a single or a plurality of abrasive elements <b>14</b>. Furthermore, the core member <b>12</b> can be completely or partially covered by the abrasive element(s) <b>14</b> in a random or designed pattern.

The de-endothelialization device <b>10</b>(<b>1</b>) described above generally has a substantially rectilinear or a curvilinear (slightly curved, i.e. having less than 360° spiral) relaxed configurations. This configuration may be referred to as a “primary shape,” i.e., referring to the basic shape of the device material. Such a device may assume folded configurations when they are subjected to an external force, e.g., buckling or compressive forces when they encounter objects.

In addition or alternatively, the vaso-occlusive device may include a “secondary relaxed shape,” which may be formed by wrapping a core member having a primary shape that is substantially linear around a shaping element. The secondary shape may be a helical coil or other shapes.

In addition or as a further alternative, the vaso-occlusive device may also assume a “tertiary relaxed shape,” which may be formed, for example, by wrapping a core member having a primary or secondary shape around a shaping element. The tertiary shape may be, for example, in a shape of a clover leaf, a twisted figure eight, a flower, a sphere, a vortex, an ovoid, or random shapes.

A secondary and/or tertiary shape may be programmed into a device using known heat treatment processes or other shape memory material properties. Once programmed, the device may be biased to a “relaxed state” including both a primary shape, secondary, and/or tertiary shape. This relaxed state may also be referred to as a lowest energy state, because, when the device is deformed into any other shape, it may store elastic energy that is removed as the device returns towards the relaxed state.

For a device that has a secondary and/or tertiary shape, the core member <b>12</b> is preferably made from a substantially resilient material, having sufficient rigidity to support the de-endothelialization device in the secondary and/or tertiary state when deployed, e.g., within an aneurysm or other body space. Thus, the space-filling capacity of these devices may be inherent within the secondary and/or tertiary relaxed shapes of these devices.

<figref idrefs="DRAWINGS">FIGS. 3 and 4</figref> illustrates de-endothelialization devices <b>10</b> having secondary shapes. These shapes are simply indicative of the various secondary shapes that may be used, and other shapes may be used as well. The device <b>10</b> illustrated in each of the <figref idrefs="DRAWINGS">FIGS. 3 and 4</figref> includes the abrasive element <b>14</b> as described previously, but is not shown for clarity.

<figref idrefs="DRAWINGS">FIG. 3</figref> depicts a de-endothelialization device <b>10</b>(<b>2</b>) having a secondary shape of a helical coil. The helical coil can have an open pitch, such as that shown in <figref idrefs="DRAWINGS">FIG. 3</figref>, or a closed pitch. <figref idrefs="DRAWINGS">FIG. 4</figref> illustrates a de-endothelialization device <b>10</b>(<b>3</b>) having a random secondary shape. Each of the secondary shapes shown in <figref idrefs="DRAWINGS">FIGS. 3 and 4</figref> may be achieved by wrapping a core member <b>12</b> having a primary shape that is substantially linear, such as that shown in <figref idrefs="DRAWINGS">FIG. 1</figref>, around a mandrel, stylet, or other shaping element. The device <b>10</b> may be subjected to a heat treatment or other step known to those skilled in the art for setting the secondary shape of the device <b>10</b>. Forming devices, such as vaso-occlusive devices, into secondary shapes is well known in the art, and need not be described in further detail.

<figref idrefs="DRAWINGS">FIGS. 5-11</figref> illustrate various de-endothelialization devices <b>10</b> of this invention having a secondary shape of a helical coil, such as that shown in <figref idrefs="DRAWINGS">FIG. 3</figref>, and a tertiary shape. These shapes are simply indicative of the various tertiary shapes that may be used, and other shapes may be used as well. While not shown, the devices <b>10</b> illustrated in each of the <figref idrefs="DRAWINGS">FIGS. 5-11</figref> include the abrasive element <b>14</b>, as discussed previously.

<figref idrefs="DRAWINGS">FIG. 5</figref> depicts a device <b>10</b>(<b>4</b>) having a tertiary shape of a clover leaf. <figref idrefs="DRAWINGS">FIG. 6</figref> depicts a device <b>10</b>(<b>5</b>) having a tertiary shape of a twisted <figref idrefs="DRAWINGS">FIG. 8</figref>. <figref idrefs="DRAWINGS">FIG. 7</figref> depicts a device <b>10</b>(<b>6</b>) having a flower-shaped tertiary shape. <figref idrefs="DRAWINGS">FIG. 8</figref> depicts a device <b>10</b>(<b>7</b>) having a substantially spherical tertiary shape. <figref idrefs="DRAWINGS">FIG. 9</figref> illustrates a device <b>10</b>(<b>8</b>) having a random tertiary shape. <figref idrefs="DRAWINGS">FIG. 10</figref> illustrates a device <b>10</b>(<b>9</b>) having tertiary shape of a vortex. <figref idrefs="DRAWINGS">FIG. 11</figref> illustrates a device <b>10</b>(<b>10</b>) having a tertiary shape of an ovoid. It should be noted that de-endothelialization device <b>10</b> may also have other secondary and tertiary shapes, and should not be limited to the examples illustrated previously. For example, the core member <b>12</b>, and accordingly, the de-endothelialization device, can be selectively sized to fill a particular aneurysm.

To make the tertiary shaped de-endothelialization devices <b>10</b>, a core member <b>12</b> that is substantially rectilinear or curvilinear may be wrapped around a mandrel or other shaping element to form a secondary shape, such as the helical coil shown in <figref idrefs="DRAWINGS">FIG. 3</figref>. The mandrel and the core member <b>12</b> may be heated to shape the core member <b>12</b> into the secondary shape. The secondary shaped core member <b>12</b>, or as in the case for the devices shown in <figref idrefs="DRAWINGS">FIGS. 5-11</figref>, the helical coil, is then wrapped around another shaping element to produce the tertiary shape. Heat may also be used to shape the core member <b>12</b> to form the tertiary shape. Stable coil designs, and methods of making such, are described in U.S. Pat. No. 6,322,576B1 to Wallace et al., the entirety of which is expressly incorporated by reference herein. It should be noted that forming devices, such as vaso-occlusive devices, into secondary and tertiary shapes is well known in the art, and need not be described in further detail.

The method of using the previously described de-endothelialization devices will now be discussed with reference to <figref idrefs="DRAWINGS">FIGS. 12-15</figref>. First, a delivery catheter <b>42</b> is inserted into the body of a patient, e.g., percutaneously through a peripheral vessel, such as a femoral, carotid, or radial artery. Other entry sites sometimes are well known to physicians who practice these types of medical procedures. The delivery catheter <b>42</b>, which may be a micro-catheter, sheath, or other elongate device, is positioned so that the distal end <b>48</b> of the delivery catheter <b>42</b> is appropriately situated, e.g., within the mouth of the body cavity <b>41</b> to be treated. The delivery catheter <b>42</b> may be advanced over or otherwise in conjunction with a guidewire, guiding catheter, or other rail, as is known in the art. In addition, the catheter <b>42</b> may be monitored, e.g., using fluoroscopy, during advancement.

Once the delivery catheter <b>42</b> is in place, the de-endothelialization device <b>10</b> may be inserted from the proximal end (not shown) of the delivery device <b>42</b> into a lumen of the delivery catheter <b>42</b>. If desired, the de-endothelialization device <b>10</b> can be heated, e.g., to a temperature above 50° C., or cooled, e.g., to a temperature below 0° C., to enhance the de-endothelializing property of the de-endothelialization device <b>10</b>. The endothelium of the aneurysm or other body lumen can be injured or destroyed simply by heating, e.g., to a temperature above 50° C., or cooling, e.g., to a temperature below 0° C., as explained further below.

For a de-endothelialization device, such as the device <b>10</b> shown in <figref idrefs="DRAWINGS">FIG. 1</figref> having no secondary shape, the de-endothelialization device <b>10</b> may naturally assume its substantially rectilinear or a curvilinear primary shape when disposed within the lumen of the delivery catheter <b>42</b>, without being subjected to substantial stress. When the de-endothelialization device <b>10</b> is disposed within the lumen of the delivery catheter <b>42</b>, the abrasive element(s) <b>14</b> may assume a bent or collapsed configuration. Alternatively, the lumen of the delivery catheter <b>42</b> can be made sufficiently wide to accommodate the de-endothelialization device <b>10</b> without substantially bending the abrasive element(s) <b>14</b>. For de-endothelialization devices having secondary and/or tertiary shapes, such as the de-endothelialization devices shown in <figref idrefs="DRAWINGS">FIGS. 3-11</figref>, they may be “stretched” or straightened to a substantially linear shape primary or secondary shape while residing within the lumen of the delivery catheter <b>42</b>, as illustrated with the de-endothelialization device <b>10</b> in <figref idrefs="DRAWINGS">FIG. 13</figref>. A de-endothelialization device that can assume a linear shape within the delivery device <b>42</b> may substantially reduce the cross-sectional dimension required of the delivery catheter <b>42</b>, which may assist advancing the catheter <b>42</b> into the body of a patient and improves the maneuverability of the catheter <b>42</b> within the body, e.g., through narrow vessels and/or tortuous anatomy.

Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 14</figref>, a de-endothelialization device having a secondary shape of a helical coil, such as the de-endothelialization device <b>10</b>, may be disposed within the lumen of a delivery catheter in an unstretched configuration. Furthermore, as shown in <figref idrefs="DRAWINGS">FIG. 15</figref>, a de-endothelialization device having a secondary shape made of a helical coil, such as the de-endothelialization device <b>10</b>, may be “stretched” from its tertiary shape into a substantially linear helical coil, when disposed within the lumen of a delivery catheter <b>42</b>.

Referring back to <figref idrefs="DRAWINGS">FIG. 12</figref>, the de-endothelialization device <b>10</b> is preferably advanced distally towards the distal end <b>48</b> of the delivery catheter <b>42</b> using a core wire or pusher member <b>44</b>. A plunger <b>46</b> may be attached to the distal end of the core wire <b>44</b> to assist advancing the de-endothelialization device <b>10</b>. Alternatively, fluid pressure may also be used to advance the de-endothelialization device <b>10</b> along the delivery catheter <b>42</b>. The inner diameter of the delivery catheter <b>42</b> should be made large enough to allow advancement of the de-endothelialization device <b>10</b>. On the other hand, the inner diameter of the delivery catheter <b>42</b> should not be significantly larger than the overall cross-sectional dimension of the de-endothelialization device <b>10</b> in order to avoid bending and kinking of the de-endothelialization device <b>10</b> within the lumen of the delivery catheter <b>42</b>.

For a de-endothelialization device having no secondary relaxed shape or having a secondary shape that is substantially rectilinear or curvilinear, such as a substantially linear helical coil, the de-endothelialization device may remain substantially rectilinear or curvilinear without undergoing substantial stress while disposed within the lumen of the delivery catheter <b>42</b>. Once the de-endothelialization device <b>10</b> or a portion of the de-endothelialization device <b>10</b> exits from the distal end <b>48</b> of the delivery catheter <b>42</b>, it may remain substantially rectilinear or curvilinear until it contacts an object, e.g., the wall of the body cavity <b>41</b>. If the de-endothelialization device <b>10</b> is advanced further distally, i.e., to introduce additional length into the body cavity, the de-endothelialization device <b>10</b> may buckle and/or bend due to the distal force exerted by the device against the object that it contacts. Consequently, the de-endothelialization device <b>10</b> may fold, thereby forming a three-dimensional structure for occupying the aneurysm. For de-endothelialization devices having secondary and/or tertiary shapes, the de-endothelialization device may attempt to assume its relaxed secondary and/or tertiary shape when ejected from the lumen of the delivery catheter <b>42</b>. The shape of the secondary and/or tertiary shapes may help fill the body cavity <b>41</b>.

Optionally, one or more additional de-endothelialization devices <b>10</b> may also be placed within the body cavity <b>41</b> by repeating the relevant steps discussed above. When a desired number of de-endothelialization devices have been placed within the body cavity <b>41</b>, the delivery catheter <b>42</b> is then withdrawn from the body cavity <b>41</b>.

During and/or after placing the de-endothelialization devices <b>10</b> in the body cavity <b>41</b>, the abrasive element(s) <b>14</b> of the de-endothelialization device(s) may disrupt the endothelium of the aneurysm, blood vessel, or other body lumen, causing the lumen wall to produce a fibro-proliferative reaction. As a result, fibrous tissue containing collagen may form at the disrupted endothelium, thereby thickening the wall of the aneurysm or body lumen. The thickening of the wall of the aneurysm or body lumen may reduce the risk of rupturing and/or growth of the aneurysm, thereby enhancing stabilization of the aneurysm, and/or enhancing stable occlusion of the aneurysm or body lumen. Eventually, an embolism may form to occlude the body cavity <b>41</b>.

<figref idrefs="DRAWINGS">FIG. 16</figref> depicts an embodiment, generally designated <b>60</b>, having a de-endothelialization device <b>10</b> that may be detached from a core wire <b>44</b> using a mechanical joint <b>64</b>. The de-endothelialization device <b>10</b> may be any one of the devices depicted in <figref idrefs="DRAWINGS">FIGS. 1-11</figref> and described above, including one or more abrasive elements <b>14</b> (not shown for clarity). Joint <b>64</b> has a clasp section <b>66</b> that remains attached to the core wire <b>44</b> when sheath or catheter body <b>42</b> is retracted proximally. Joint <b>64</b> also includes a second clasp section <b>68</b> that is carried on the proximal end of the de-endothelialization device <b>10</b> and interlocks with clasp section <b>66</b> when the assembly is within sheath <b>42</b>. When the sheath <b>42</b> is withdrawn from about the assembly, the clasp sections are free to disengage, thus detaching the de-endothelialization device <b>10</b>. Core wire <b>44</b> may be electrically connected to a source of radiofrequency energy.

The de-endothelialization devices <b>10</b> described herein may also be non-detachable or detachable by electrolytic joints or connectors, such as those described in U.S. Pat. Nos. 5,234,437, 5,250,071, 5,261,916, 5,304,195, 5,312,415, and 5,350,397, the entireties of which are expressly incorporated by reference herein.

<figref idrefs="DRAWINGS">FIG. 17</figref> shows an embodiment, generally designated <b>70</b>, having a de-endothelialization device <b>10</b> that may be detached from a core wire <b>44</b> using a joint <b>74</b> susceptible to electrolysis. The de-endothelialization device <b>10</b> may be any one of the devices depicted in <figref idrefs="DRAWINGS">FIGS. 1-11</figref> and described above, including one or more abrasive elements <b>14</b> (not shown for clarity). Such joints are described in detail in U.S. Pat. No. 5,423,829, the entirety of which is expressly incorporated by reference herein. Joint <b>74</b> may be made of a metal that, upon application of a suitable voltage to the core wire <b>44</b>, may erode in the bloodstream, thereby allowing the de-endothelialization device <b>10</b> to detach. The de-endothelialization device <b>10</b> may be made of a metal that is more “noble” in the electromotive series than the metal of joint <b>74</b>. A return electrode (not shown) may be supplied to complete the circuit, as is well know to those skilled in the art. The region of core wire <b>44</b> proximal to the joint <b>74</b> may be insulated to focus the erosion at the joint <b>74</b>. An electrically conductive bushing <b>76</b> is used to connect the distal end of core wire <b>44</b> to the proximal end of the de-endothelialization device <b>10</b>.

For a de-endothelialization device <b>10</b> that is detachably coupled to the core wire <b>44</b> (such as those illustrated in <figref idrefs="DRAWINGS">FIGS. 16 and 17</figref>), the de-endothelialization device <b>10</b> may be moved, i.e., advanced, retracted, and/or rotated, within the aneurysm or other body lumen by manipulating (i.e., advancing, retracting, and/or rotating) the proximal end of the core wire <b>44</b>. Moving the de-endothelialization device <b>10</b> within the aneurysm or other body lumen may increase the surface area of the endothelium disrupted by the abrasive element(s) <b>14</b> of the de-endothelialization device <b>10</b>. After the endothelium of the aneurysm or other body lumen has been sufficiently, disrupted, the de-endothelialization device <b>10</b> may be de-coupled from the core wire <b>44</b>. If desired, one or more additional de-endothelialization device(s) <b>10</b> may be inserted into the aneurysm or other body lumen, as discussed previously.

Although, the de-endothelialization device <b>10</b> described previously is adapted to be implanted in a body cavity, such needs not be the case. After the endothelium of the aneurysm or other body lumen has been disrupted, the de-endothelialization device <b>10</b> may be removed from the aneurysm or other body lumen by retracting the proximal end of the core wire <b>44</b>, thereby causing the de-endothelialization device <b>10</b> to move back into the lumen of the catheter body <b>42</b>. As such, the de-endothelialization device <b>10</b> may be used as a tool without being implanted in a body cavity. Thereafter, one or more vaso-occlusive devices may be delivered to fill the aneurysm or other body lumen. If the aneurysm or other body lumen is small, the de-endothelialization of the aneurysm may cause the wall to thicken enough to occlude the aneurysm or other body lumen without using a vaso-occlusive device. De-endothelialization devices not intended for implantation are described further below.

B. Non-Implantable De-Endothelialization Devices

<figref idrefs="DRAWINGS">FIGS. 18-24</figref> show variations of a de-endothelialization device <b>100</b> that is adapted to be removed from an aneurysm or other body lumen after an endothelium of the aneurysm or other body lumen has been disrupted.

<figref idrefs="DRAWINGS">FIG. 18</figref> shows a de-endothelialization device <b>100</b>(<b>1</b>) having a core member <b>102</b> and one or more abrasive elements <b>104</b> coupled to the core member <b>102</b>. The abrasive element(s) <b>104</b> may be any of the variations of the abrasive element <b>14</b> discussed previously. Any of the materials discussed previously with reference to the core member <b>12</b> may also be used to construct the core member <b>102</b>. The core member <b>102</b> is preferably detachably coupled to a distal end <b>112</b> of an elongate member, such as a core wire or a pusher member <b>114</b>. Thus, if the core member <b>102</b> becomes irretrievable during a procedure, the core member <b>102</b> can be decoupled from the elongate member <b>114</b>, and left within the aneurysm or other body lumen as an implant. Alternatively, the core member <b>102</b> may be secured to the distal end <b>112</b> of the elongate member <b>114</b> by a suitable adhesive, which may depend upon the materials from which the elongate member <b>114</b> and the core member <b>102</b> are made. The core member <b>102</b> may also be fabricated together with the elongate member <b>114</b> as one unit during manufacturing. In this case, the core member <b>102</b> would include the elongate member <b>114</b>. A handle <b>116</b> may optionally be secured to a proximal end <b>118</b> of the elongate member <b>114</b>.

The core member <b>102</b> and/or the distal end <b>112</b> of the elongate member <b>114</b> may assume a substantially linear shape, such as that shown in <figref idrefs="DRAWINGS">FIG. 18</figref>. Alternatively, the core member <b>102</b> may also assume a relaxed configuration that has a curvilinear shape, such as a J-shape (<figref idrefs="DRAWINGS">FIG. 19</figref>), a spiral (<figref idrefs="DRAWINGS">FIG. 20</figref>), or other designed shapes. In general, any of the shapes-discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 1-11</figref> may also be used for the core member <b>102</b>. Although not required, the de-endothelialization device <b>100</b>(<b>1</b>) may optionally include a tubular element <b>120</b> (such as a sheath or a catheter) capable of coaxially surrounding the core member <b>102</b> during a procedure. The core member <b>102</b> and/or the distal end <b>112</b> of the elongate member <b>114</b> assumes a low profile configuration when disposed within a lumen <b>122</b> of the tubular element <b>120</b>. If the core member <b>102</b> and/or the distal end <b>112</b> of the elongate member <b>114</b> has a non-linear relaxed configuration, the core member <b>102</b> and/or the distal end <b>102</b> may assume its relaxed configuration when deployed from the tubular element <b>120</b>.

Turning to <figref idrefs="DRAWINGS">FIG. 21A</figref>, optionally, the de-endothelialization device <b>100</b> may include a steering mechanism <b>130</b> for changing the shape of the distal end <b>112</b> of the elongate member <b>104</b>. The steering mechanism <b>130</b> can vary. For example, <figref idrefs="DRAWINGS">FIG. 21</figref> shows a steering mechanism as disclosed in U.S. application Ser. No. 07/789,260, now U.S. Pat. No. 5,363,861 issued Nov. 15, 1994, the entirety of which is expressly incorporated by reference herein. As <figref idrefs="DRAWINGS">FIG. 21B</figref> shows, the steering mechanism <b>130</b> may include a rotating cam wheel <b>132</b> within the handle <b>116</b>, and an external steering lever or control (not shown) may rotate the cam wheel <b>132</b>. The cam wheel <b>132</b> holds the proximal ends of right and left steering wires <b>136</b> and <b>138</b>. The steering wires <b>136</b> and <b>138</b> may extend along the associated left and right side surfaces of the cam wheel <b>132</b> and through the guide tube <b>140</b>. The steering wires <b>136</b> and <b>138</b> connect to left and right sides of a resilient bendable wire or spring within a distal section of the elongate member <b>104</b>. Alternatively, the steering wires <b>136</b> and <b>138</b> may connect to a portion of the core member <b>102</b>.

As <figref idrefs="DRAWINGS">FIG. 21A</figref> shows, manipulating the steering lever or control causes the distal end <b>112</b> of the elongate member <b>104</b> and/or the core member <b>102</b> to bend up or down. By rotating the handle, thereby bending the distal end <b>112</b> of the elongate member <b>104</b>, and by manipulating the steering lever, it is possible to maneuver the distal end <b>112</b> of the elongate member <b>104</b> virtually in any direction. The steerable section simplifies the positioning of the distal end <b>102</b>, and accordingly, the core member <b>102</b> of the de-endothelialization device <b>100</b>.

When using the de-endothelialization device <b>100</b>, the distal end <b>112</b> (including the de-endothelialization device <b>100</b>) of the elongate member <b>104</b> is first positioned inside an aneurysm or other body lumen. Positioning the distal end <b>112</b> of the elongate member <b>104</b> may be facilitated using a guide wire and/or sheath (such as the tubular element <b>120</b>), as is known to those skilled in the art. If desired, the de-endothelialization device <b>100</b> may be heated or cooled to a certain temperature to enhance the de-endothelializing capability of the de-endothelialization device <b>100</b>, as discussed previously. Next, by manipulating (i.e., advancing, retracting, and/or turning) the proximal end <b>118</b> of the elongate member <b>104</b> (or the handle <b>116</b> if one is provided), the core member <b>102</b> of the de-endothelialization device <b>100</b> may be positioned at various locations against the endothelium of the aneurysm or other body lumen, thereby disrupting the endothelium of the various locations of the aneurysm or other body lumen. If a steering mechanism <b>130</b> is provided, the steering mechanism <b>130</b> may also be used to position the core member <b>102</b> of the de-endothelialization device <b>100</b>.

After the abrasive element <b>104</b> of the de-endothelialization device <b>100</b> has disrupted sufficient surface area of the endothelium of the aneurysm or other body lumen, the de-endothelialization device <b>100</b> may be withdrawn from the aneurysm or other body lumen. After some time, fibrous tissue may form at the disrupted endothelium, causing the wall of the aneurysm or other body lumen to thicken, as discussed above with reference to implantable de-endothelialization devices. For an aneurysm or other body lumen having a certain size, it may be desirable to deliver one or more vaso-occlusive device(s) into the aneurysm or other body lumen after the de-endothelialization device <b>100</b> has been removed from the aneurysm or other body lumen. Alternatively, if the aneurysm or other body lumen is small, the de-endothelialization of the aneurysm or other body lumen may cause the wall to thicken enough to occlude the aneurysm or other body lumen without requiring a vaso-occlusive device to be implanted.

In certain situations, it may be desirable to disrupt the neck of an aneurysm, with or without de-endothelializing the wall of the aneurysm sac. For example, when the neck of an aneurysm is small, de-endothelializing just the neck may cause the neck of the aneurysm to thicken, thereby closing the neck. For a wide neck aneurysm, de-endothelializing the neck of the aneurysm may have the benefit of reducing the size of the neck. It should be noted that the embodiments of de-endothelialization devices described above may also be suitable for disrupting the neck of an aneurysm, and that the methods described above may be used for this purpose.

<figref idrefs="DRAWINGS">FIGS. 22-24</figref> show variations of a de-endothelialization device <b>100</b>, including an expandable member coupled to a core wire or other elongate member <b>114</b>. <figref idrefs="DRAWINGS">FIG. 22A</figref> shows a de-endothelialization device <b>100</b>(<b>2</b>) including one or more abrasive elements <b>104</b>, and an expandable basket <b>150</b>. Although the expandable basket <b>150</b> is shown to include two flexible wires <b>152</b>, it may include any number of wires <b>152</b>. Furthermore, the basket <b>150</b> is not necessarily limited to the example illustrated in <figref idrefs="DRAWINGS">FIG. 22</figref>. Alternatively, the basket <b>150</b> may include a braided structure or a mesh. The basket <b>150</b> is preferably made of an elastic material, such as nitinol, although other materials may also be used. The distal end of the basket <b>150</b> may be secured to the elongate member <b>114</b> such that rotating the proximal end <b>118</b> of the elongate member <b>114</b> may cause the expandable basket <b>150</b> to rotate. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 23</figref>, the distal end of the expandable basket <b>150</b> may be rotatably secured to the elongate member <b>114</b> so that the basket <b>150</b> can rotate about the elongate member <b>114</b>. In either case, the basket <b>150</b> may be rotated manually or automatically, e.g., by a machine.

As shown in <figref idrefs="DRAWINGS">FIGS. 22A and 22B</figref>, the basket <b>150</b> may assume a low or collapsed profile while disposed within the lumen of the tubular element <b>120</b>, and is free to assume an expanded profile when it is outside the tubular element <b>120</b>. The basket <b>150</b> may be self-expanding or self-collapsing. A self-expanding basket has a relaxed expanded configuration, and may be collapsed by directing opposite ends <b>154</b> and <b>156</b> of the wires <b>152</b> (or the elements defining the basket <b>150</b>) further from one another. A self-collapsing basket has a relaxed collapsed (or unexpanded) configuration, and may be expanded by directing opposite ends <b>154</b> and <b>156</b> of the wires <b>152</b> (or the elements defining the basket <b>150</b>) closer towards one another. The shape of the basket <b>150</b> may be changed, for example, by varying the tension or compression on any or all of the wires <b>152</b> via a control (not shown). <figref idrefs="DRAWINGS">FIGS. 22A and 22B</figref> show that the elongate member <b>114</b> is substantially linear. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 24</figref>, the distal end <b>112</b> of the elongate member <b>114</b> may be bent or preformed such that it forms an angle <b>160</b> with an axis <b>162</b> of a proximal portion of the elongate member <b>114</b>. Expandable baskets that may be used are described in U.S. Pat. Nos. 5,893,847, 5,925,038, and 6,216,044, the disclosures of which are expressly incorporated by reference herein.

<figref idrefs="DRAWINGS">FIG. 25A</figref> shows a de-endothelialization device <b>100</b>(<b>3</b>) that includes a plurality of abrasive elements <b>104</b> carried by a balloon <b>170</b>. The balloon <b>170</b> has a proximal end <b>171</b> coupled to a distal end <b>172</b> of a core tube <b>174</b>. The core tube <b>174</b> also includes a proximal end <b>176</b>, an opening <b>177</b> at the proximal end <b>176</b>, and a lumen <b>178</b> (not shown) extending between the distal end <b>172</b> and the proximal end <b>176</b>.

The proximal end <b>171</b> of the balloon <b>170</b> is preferably detachably coupled to the distal end <b>172</b> of the core tube <b>174</b> by a joint <b>180</b>, such as an electrolytic joint or a mechanical joint, as discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 16 and 17</figref>. This may allow the balloon <b>170</b> to be de-coupled from the core tube <b>174</b> if the balloon <b>170</b> cannot be retrieved during a procedure. The balloon <b>170</b> may also be secured to the distal end <b>172</b> of the core tube <b>174</b> by a glue or other suitable adhesive. Alternatively, the balloon <b>170</b> can be fabricated with the core tube <b>174</b> as one unit during manufacturing. Optionally, the de-endothelialization device <b>100</b>(<b>3</b>) may include the core tube <b>174</b>. The endothelialization device <b>100</b>(<b>3</b>) may also optionally include a tubular element <b>182</b>, such as a sheath or a catheter, that is capable of surrounding the core tube <b>174</b> and the balloon <b>170</b> when it is un-inflated.

The balloon <b>170</b> is preferably made of thermoplastic or elastomeric materials, such as polyimide (kapton), polyester, silicone rubber, nylon, mylar, polyethylene, or polyvinyl chloride. However, other elastic or inelastic materials known in the art may also be used for constructing the balloon <b>170</b>. Expandable balloons have been described in U.S. Pat. No. 5,925,083, the entirety of which is expressly incorporated by reference herein.

It should be noted that the shape of the expandable member (i.e., the basket <b>150</b> or the balloon <b>170</b>) is not necessarily limited to those illustrated in the figures, and other shapes may also be used. Furthermore, various patterns may be formed by the abrasive element(s) <b>104</b> on the surface of the expandable member so that only a desired portion of the endothelium of the aneurysm or other body lumen is disrupted. <figref idrefs="DRAWINGS">FIG. 25B</figref> shows a balloon <b>170</b> wherein only the distal end of the balloon <b>170</b> is covered by the abrasive elements <b>104</b>. Other patterns of the abrasive element(s) <b>104</b> may also be used.

When using a de-endothelialization device <b>100</b> having an expandable member (i.e., the basket <b>150</b> or the balloon <b>170</b>), the tubular element <b>182</b> is first positioned so that the distal end of the tubular element <b>182</b> is adjacent to a neck of an aneurysm or at the site of another body lumen to be de-endothelialized. The tubular element <b>182</b> may be placed using a guide wire or other rail, as is known in the art. The expandable member is initially collapsed and placed within the lumen of the tubular element <b>182</b>. The expandable member may be inserted into a lumen <b>184</b> of the tubular element <b>182</b> after the distal end of the tubular element <b>182</b> has been placed adjacent to the neck of the aneurysm or at the site of another body lumen to be de-endothelialized. Alternatively, the expandable member may be inserted into the lumen <b>184</b> of the tubular element <b>182</b> first, and the tubular element <b>182</b> carrying the expandable member may then be placed into a vessel leading to the aneurysm or at the site of another body lumen to be de-endothelialized.

The distal tip of the tubular element <b>182</b> is preferably placed within the aneurysm or at the site of another body lumen to be de-endothelialized. However, the distal tip of the tubular element <b>182</b> may also be placed outside the aneurysm adjacent to the neck of the aneurysm so long as the expandable member can be deployed into the aneurysm, or placed adjacent to the segment of vessel to be de-endothelialized so long as the expandable member can be deployed into the segment of vessel to be de-endothelialized. When the distal tip of the tubular element <b>182</b> is positioned as desired, the expandable member is then expanded. For the de-endothelialization device <b>100</b> including the balloon <b>170</b>, the balloon <b>170</b> is expanded by delivering a fluid through the opening <b>177</b> and into the lumen <b>178</b> of the core tube <b>174</b>. The core tube <b>174</b> delivers the fluid into an interior of the balloon <b>170</b>, thereby expanding the balloon <b>170</b>. The fluid can be a gas or a liquid, such as water, saline, or blood. A radio-opaque marker (not shown) may be carried at the distal end of the tubular element <b>182</b> and/or the expandable member to help positioning the tubular element <b>182</b> and/or the expandable member relative to the aneurysm or other body lumen.

If the expandable member has an expanded shape that substantially occupies an aneurysm or other body lumen, the abrasive elements <b>104</b> may disrupt the endothelium of the aneurysm or other body lumen when the expandable member is expanded. The expandable member may also have an expanded shape that is slightly larger than the aneurysm or other body lumen to enhance the de-endothelialization property of the de-endothelialization device <b>100</b>. After the endothelium of the aneurysm or other body lumen is disrupted, the expandable member is then collapsed and removed from the aneurysm or other body lumen.

Alternatively, before the expandable member is collapsed, the expandable member may be moved within the aneurysm or other body lumen by manipulating the handle <b>116</b>, thereby causing further disruption to the endothelium of the aneurysm or other body lumen. After the abrasive element <b>104</b> of the de-endothelialization device <b>100</b> has disrupted a sufficient area of the endothelium of the aneurysm or other body lumen, the de-endothelialization device <b>100</b> may then be withdrawn from the aneurysm or other body lumen.

II. De-Endothelialization Using Thermal Treatment

A. De-Endothelialization Using a Heated or Cooled Implant

The endothelium of an aneurysm can also be disrupted by altering the temperature of the endothelium. As mentioned previously, the endothelium of an aneurysm or other body lumen can be injured or destroyed at a temperature that is above 50° C. or below 0° C. <figref idrefs="DRAWINGS">FIG. 26</figref> shows an example of a de-endothelialization device <b>200</b> adapted to be heated or cooled to a de-endothelializing temperature. The de-endothelialization device <b>200</b> can be a variety of objects, such as a vaso-occlusive device, so long as it is capable of reaching a temperature that is sufficient for disrupting an endothelium of an aneurysm or other body lumen. The de-endothelialization device <b>200</b> can be thermally treated by placing it in a freezer or in an oven. Alternatively, the de-endothelialization device <b>200</b> can also be thermally treated by placing it in a media, such as water or saline, that has been heated or cooled. Other methods known in the art for altering a temperature of an object can also be used.

The de-endothelialization device <b>200</b> can have a variety of shapes or forms. The de-endothelialization device <b>200</b> preferably has a relaxed, secondary shape of a helical coil, as shown in <figref idrefs="DRAWINGS">FIG. 26</figref>. However, any of the shapes discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 1-11</figref> is also applicable to the de-endothelialization device <b>200</b>. In particular, the de-endothelialization device <b>200</b> can have a tertiary shape. The de-endothelialization device <b>200</b> can also include an expandable member, such as a balloon or a basket, as discussed previously. Other shapes of devices capable of being placed within a body cavity may also be used, as are known in the art.

The de-endothelialization device <b>200</b> should be made from a material that can maintain its structural integrity in a de-endothelializing temperature. That is, the de-endothelialization device <b>200</b> should be made from a material such that it will not melt or become too brittle when subjected to the desired thermal treatment. In general, because of their high thermal conductivity, metals are preferable materials for constructing the de-endothelialization device <b>200</b>. Also, any of the materials discussed previously with reference to the core member <b>12</b> of the de-endothelialization device <b>10</b> can also be used, so long as the de-endothelialization device <b>200</b> remains deliverable to an aneurysm after thermal treatment. Other materials known in the art may also be used for the constructing the de-endothelialization device <b>200</b>.

<figref idrefs="DRAWINGS">FIG. 27</figref> shows a de-endothelialization device <b>200</b>(<b>1</b>) that is adapted to be thermally treated before it is delivered to an aneurysm or other body lumen. A tubular element <b>210</b>, such as a sheath or a catheter, is used to deliver the vaso-occlusive device <b>200</b>(<b>1</b>) to an aneurysm or other body lumen. The tubular element <b>210</b> includes an insulative layer <b>212</b> at an interior surface of the tubular element <b>210</b>. The insulative layer <b>212</b> prevents or reduces the amount of thermal transfer from the de-endothelialization device <b>200</b>(<b>1</b>) to an exterior surface <b>214</b> of the tubular element <b>210</b>. The insulative layer <b>212</b> is preferably made of a polymer. However, other materials having desired thermal insulation properties known in the art may also be used. If the tubular element <b>210</b> is made from a material that possesses desired thermal insulation properties, then the insulative layer <b>212</b> becomes optional, and is not required.

<figref idrefs="DRAWINGS">FIG. 27</figref> shows that the de-endothelialization device <b>200</b> has a secondary shape of a helical coil when disposed within the lumen of the tubular element <b>210</b>. However, as discussed previously, such needs not to be the case. As shown in <figref idrefs="DRAWINGS">FIG. 28</figref>, the de-endothelialization device <b>200</b>(<b>1</b>) can also be stretched to a substantially linear or curvilinear shape when disposed within the lumen of the tubular element <b>210</b>. The method of delivering the de-endothelialization device <b>200</b>(<b>1</b>) is similar to that discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 12-15</figref>.

<figref idrefs="DRAWINGS">FIG. 29A</figref> shows a de-endothelialization device <b>200</b>(<b>2</b>) that is adapted to be heated after it has been placed within an aneurysm or other body lumen. The de-endothelialization device <b>200</b>(<b>2</b>) may optionally include a tubular element <b>224</b>, such as a sheath or a catheter. The de-endothelialization device <b>200</b>(<b>2</b>) is electrically coupled to a core wire <b>220</b> that delivers electrical energy from a source of electrical energy, such as a radio frequency (RF) generator <b>222</b>, to the device <b>200</b>(<b>2</b>). The de-endothelialization device <b>200</b>(<b>2</b>) acts as a resistor and converts the electrical energy to heat. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 29B</figref>, the de-endothelialization device <b>200</b>(<b>2</b>) may be mechanically coupled to a heatable element <b>223</b>. The heatable element <b>223</b> may act as a resistor and convert electrical energy from the generator <b>222</b> to heat. Because of the mechanical coupling between the heatable element <b>223</b> and the de-endothelialization device <b>200</b>(<b>2</b>), heat flows from the heatable element <b>223</b> to the de-endothelialization device <b>200</b>(<b>2</b>) by conduction.

When using the de-endothelialization device <b>200</b>(<b>2</b>), the de-endothelialization device <b>200</b>(<b>2</b>) is first placed within the aneurysm or other body lumen by any conventionally known method. For example, the tubular element <b>224</b> may first be inserted into a vasculature of a patient such that the distal end of the tubular element <b>224</b> is adjacent to an aneurysm or other body lumen. The de-endothelialization device <b>200</b>(<b>2</b>) can then be delivered to the aneurysm or other body lumen via the tubular element <b>224</b>.

Once positioned within the aneurysm or other body lumen, the de-endothelialization device <b>200</b>(<b>2</b>) is then heated. When the temperature of the de-endothelialization device <b>200</b>(<b>2</b>) reaches a desired level, the de-endothelialization device <b>200</b>(<b>2</b>) can then be de-coupled from the core wire <b>220</b> by methods that are described previously. The tubular element <b>224</b> and/or the core wire <b>220</b> may optionally include a sensor, such as a thermistor, to monitor the temperature at the distal end of the core wire <b>220</b>.

Although the de-endothelialization device <b>200</b>(<b>2</b>) is adapted to be deployed within a body cavity as an implant, such needs not be the case. After the endothelium of the aneurysm or other body lumen has been sufficiently disrupted by the heated de-endothelialization device <b>200</b>(<b>2</b>), the de-endothelialization device <b>200</b>(<b>2</b>) can be removed from the aneurysm or other body lumen by retracting a proximal end of the core wire <b>220</b>, thereby causing the de-endothelialization device <b>200</b>(<b>2</b>) to retract back into the lumen of a tubular element <b>224</b>. As such, the de-endothelialization device <b>200</b>(<b>2</b>) may also be used as a tool without being implanted in a body cavity. One or more vaso-occlusive devices may then be delivered to fill the aneurysm or other body lumen. If the aneurysm or other body lumen is small, the de-endothelialization of the aneurysm may cause the wall to be thicken enough to occlude the aneurysm without using a vaso-occlusive device.

B. De-Endothelialization Using a Heat Delivery Device

<figref idrefs="DRAWINGS">FIG. 30</figref> shows a de-endothelialization device <b>300</b> that is adapted to deliver heat energy to an endothelium of an aneurysm. The de-endothelialization device <b>300</b> includes an operative element <b>302</b> and an elongate member <b>304</b> having a distal end <b>306</b> and a proximal end <b>308</b>. The operative element <b>302</b> is carried at the distal end <b>306</b> of the elongate member <b>304</b>, and is adapted to be electrically coupled to a generator <b>310</b>. Optionally, the de-endothelialization device <b>300</b> may include a sheath <b>312</b> having a lumen <b>314</b> within which the distal end <b>306</b> of the member <b>304</b> may slide. Optionally, the de-endothelialization device <b>300</b> may also include a steering mechanism, such as that shown in <figref idrefs="DRAWINGS">FIGS. 21A and 21B</figref> and described above, to facilitate positioning the operative element <b>302</b>.

The operative element <b>302</b> may have a variety of shapes. In general, any of the shapes discussed previously with reference to the de-endothelialization devices <b>10</b> shown in <figref idrefs="DRAWINGS">FIGS. 1-11</figref> may be used for the operative element <b>302</b>. The operative element <b>302</b> may also include an expandable basket such as that shown in <figref idrefs="DRAWINGS">FIGS. 22-24</figref>, in which case each of the wires <b>152</b> (or the elements making up the basket) may be selectively heated. Alternatively, the operative element <b>302</b> may include a balloon, such as that shown in <figref idrefs="DRAWINGS">FIG. 25A</figref>, in which case the balloon may be heated by supplying and/or circulating heated fluid within the balloon. Cooled fluid may also be used if it is desirable to disrupt the endothelium of an aneurysm or other body lumen using balloon that is below a certain temperature.

When using the de-endothelialization device <b>300</b>, the operative element <b>302</b> is first inserted into a vein or an artery and positioned within an aneurysm or other body lumen. The sheath <b>312</b> and/or a guide wire may be used to facilitate positioning the operative element <b>302</b>, as is known in the art. The de-endothelialization device <b>300</b> may optionally include a radio-opaque marker on a distal portion of the member <b>304</b> and/or the sheath <b>312</b>, so that the position of the device can be monitored during the procedure. The operative element <b>302</b> may receive electrical energy from the generator <b>310</b>, and convert the electrical energy generated by the generator <b>310</b> to heat.

The operative element <b>302</b> may be used to deliver heat to the endothelium of an aneurysm or other body lumen by convection or conduction. Delivering heat to the endothelium by convection does not require the operative element <b>302</b> to directly contact the endothelium of the aneurysm or other body lumen. Rather, heat is transferred from the operative element <b>302</b> to the endothelium by the medium, such as blood, that is between the operative element <b>302</b> and the endothelium. On the other hand, delivering heat to the endothelium by conduction may require the operative element <b>302</b> to contact the endothelium of the aneurysm or other body lumen. In either case, the amount of heat generated by the operative element <b>302</b> should be sufficient such that the endothelium of the aneurysm or other body lumen is disrupted. The distal end of the elongate member <b>304</b> may optionally include a sensor, such as a thermistor, to detect a temperature of the operative element <b>302</b>. After the de-endothelialization process, the operative element <b>302</b> of the de-endothelialization device <b>300</b> is then removed from the aneurysm or other body lumen.

C. De-Endothelialization Using a Heat Producing or Cooling Chemical

The endothelium of an aneurysm or other body lumen may also be disrupted by a heat producing chemical. For example, a dual lumen catheter may be used to deliver two fluids, such as calcium chloride and water, that, when mixed, undergo a chemical reaction that produces heat. Alternatively, fluids such as ammonium nitrate and water, known to cause a cooling reaction when mixed may also be used. U.S. patent application Ser. No. 10/150,456, the disclosure of which is expressly incorporated by reference herein, describes a dual lumen catheter that may be suitable for delivering the two heat producing fluids. Other commercially available dual lumen catheters may also be used. Alternatively, a single lumen catheter may be used to deliver the two fluids, sequentially or alternately, to an aneurysm or other body lumen.

III. De-Endothelialization Using a Fluid

A. Delivery of De-Endothelialization Fluid Using a Fluid Delivery Device

The endothelium of an aneurysm or other body lumen may also be disrupted using a fluid <b>350</b> that is delivered to the endothelium of the aneurysm. As used herein, “fluid” refers to both liquid and gas. The fluid <b>350</b> may be a heated or cooled liquid, such as water or saline. The fluid <b>350</b> may also contain any cytotoxic agent including, but not limited to oxidized LDL, perforins, toxin-conjugated antibodies to the endothelial cells, antibodies to the complement protective proteins decay accelerating factor (DAF) (also known as CD55), homologous restriction factor (also known as CD59), membrane cofactor protein (MCP) (also known as CD46), mitochondrial inhibitors, inhibitors of cell membrane ion-pumps, hypotonic fluid, hypertonic solution, CD4 T cells, and/or agents that induce apoptosis/Fas receptor agonists. Enzymes, such as tryspin or collagenase, that are capable of chemically removing the endothelial cells from its basement membranes can also be used. The fluid <b>350</b> can also be other drugs, medications, solutions, that are known in the art for disrupting cells or tissues.

<figref idrefs="DRAWINGS">FIG. 31</figref> shows a de-endothelialization fluid delivery device <b>360</b>(<b>1</b>) that includes a delivery tube <b>362</b> having a distal end <b>364</b>, a proximal end <b>366</b>, and a lumen <b>368</b> extending between the distal end <b>364</b> and the proximal end <b>366</b>. The delivery tube <b>362</b> may be a catheter, micro catheter, or sheath capable of being inserted into a vasculature of a mammal. The distal end <b>364</b> of the delivery tube <b>362</b> is adapted to be placed adjacent or within an aneurysm or other body lumen, while the proximal end <b>366</b> of the delivery tube <b>362</b> is adapted to be coupled to a fluid source <b>370</b>. The de-endothelialization fluid delivery device <b>360</b> may optionally include the fluid source <b>370</b>. The fluid source <b>370</b>, which includes a container such as a syringe, a bag, a bottle, or any fluid-holding device, contains the fluid <b>350</b> that is capable of disrupting an endothelium of an aneurysm or other body lumen, as discussed previously.

When using the de-endothelialization fluid delivery device <b>360</b>, the distal end <b>364</b> of the delivery tube <b>362</b> is first placed within the aneurysm or other body lumen. The distal end of the delivery tube <b>362</b> may optionally include a radio-opaque marker to assist positioning the delivery tube <b>362</b>. When the delivery tube <b>362</b> is positioned as desired, the fluid <b>350</b> is then delivered from the fluid source <b>370</b> to within the aneurysm or other body lumen. Optionally, the fluid source <b>370</b> may include a pump or syringe for pressurizing the fluid <b>350</b> during the procedure. After the fluid <b>350</b> contacts the endothelium of the aneurysm or other body lumen, the de-endothelialization property of the fluid <b>350</b> causes the endothelium of the aneurysm or other body lumen to be disrupted. When a desired amount of the fluid <b>350</b> has been delivered, the distal end <b>364</b> of the delivery tube <b>362</b> is then withdrawn from the aneurysm or other body lumen.

In certain situations, it may be desirable to prevent the fluid <b>350</b> from leaving the aneurysm or other body lumen once the fluid <b>350</b> has been delivered into the aneurysm or other body lumen. <figref idrefs="DRAWINGS">FIG. 32</figref> shows a de-endothelialization fluid delivery device <b>360</b>(<b>2</b>) wherein the distal end <b>364</b> of the delivery tube <b>362</b> has a diameter <b>380</b> that is substantially the same or slightly larger than a diameter of an aneurysm or other body lumen. In this case, after the fluid <b>350</b> has been delivered to the aneurysm, most or all of the excess fluid <b>350</b> may flow back into the lumen <b>368</b> of the delivery tube <b>362</b>. Optionally, a source of vacuum (not shown) may be coupled to the lumen <b>368</b> to aspirate fluid from the aneurysm or other body lumen.

<figref idrefs="DRAWINGS">FIG. 33A</figref> shows another de-endothelialization fluid delivery device <b>360</b>(<b>3</b>) that includes one or more drainage ports <b>390</b> at the distal end <b>364</b> of the delivery tube <b>362</b>. The delivery tube <b>362</b> further includes a drainage lumen <b>392</b> that is in fluid communication with the drainage port(s) <b>390</b>. The de-endothelialization fluid delivery device <b>360</b>(<b>3</b>) also has a distal end diameter <b>380</b> that is substantially the same or slightly larger than a diameter of an aneurysm. The drainage ports <b>390</b> are located proximal to the distal tip of the delivery tube <b>362</b>. <figref idrefs="DRAWINGS">FIG. 33B</figref> shows a variation of the construction of the delivery tube <b>362</b> in which the drainage port <b>390</b> is also proximal to the distal tip of the delivery tube <b>362</b>.

When using the de-endothelialization device <b>360</b>(<b>3</b>), the distal end <b>364</b> of the delivery tube <b>362</b> is inserted into an aneurysm such that the drainage port(s) <b>390</b> is in fluid communication with an interior of the aneurysm. After the fluid <b>350</b> has been delivered to the aneurysm through the lumen <b>368</b> of the delivery tube <b>362</b>, most or all of the excess fluid <b>350</b> may flow back into the drainage lumen <b>392</b> of the delivery tube <b>362</b> through the drainage port(s) <b>390</b>.

<figref idrefs="DRAWINGS">FIG. 33A</figref> shows that the drainage port <b>390</b> is located transversely at a wall of the delivery tube <b>362</b>. However, the drainage port <b>390</b> may also be located elsewhere. As shown in <figref idrefs="DRAWINGS">FIG. 33C</figref>, the drainage port <b>390</b> may also be located at the distal tip of the delivery tube <b>362</b>. It should be noted that the number of drainage ports <b>390</b> may vary. Furthermore, the usage of the lumen <b>368</b> of the delivery tube <b>362</b> and the lumen <b>392</b> may interchange. In an alternative embodiment, the lumen <b>392</b> may be used to delivery fluid <b>350</b> to an aneurysm, and the lumen <b>368</b> of the delivery tube <b>362</b> may be used to drain or aspirate fluid <b>350</b> from the aneurysm.

The previously illustrated embodiments show that the drainage lumen <b>368</b> is defined within the wall of the delivery tube <b>362</b>. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 33D</figref>, the delivery tube <b>362</b> may include an inner tube <b>394</b> placed coaxially within the lumen <b>368</b> of the delivery tube <b>362</b>. The inner tube <b>394</b> has a lumen <b>396</b> that is in fluid communication with one or more drainage ports <b>390</b> located at the distal end <b>364</b> of the delivery tube <b>362</b>. Excess fluid <b>350</b> from the aneurysm may be drained into the drainage port <b>390</b> and delivered to a proximal end via the lumen <b>396</b> of the inner tube <b>394</b>. Alternatively, the inner tube <b>394</b> may be used to deliver fluid <b>350</b> to the aneurysm and the lumen <b>368</b> of the delivery tube <b>362</b> may be used to aspirate excess fluid <b>350</b> from the aneurysm to a proximal end of the tube <b>362</b>.

<figref idrefs="DRAWINGS">FIG. 34A</figref> shows another de-endothelialization fluid delivery device <b>360</b>(<b>4</b>) that includes the delivery tube <b>362</b> and a sealing member or stopper <b>400</b> secured to the distal end <b>364</b> of the delivery tube <b>362</b>. The device <b>360</b>(<b>4</b>) may include one or more drainage ports (not shown) in accordance with any of the embodiments described above. The stopper <b>400</b> is used to substantially seal the aneurysm, i.e., to prevent or reduce the risk of having fluid <b>350</b> delivered into the aneurysm from escaping into the artery or vein <b>402</b>. As such, the diameter <b>380</b> of the delivery tube <b>362</b> may be substantially the same or smaller than a diameter of the aneurysm, as discussed previously with reference to <figref idrefs="DRAWINGS">FIG. 32</figref>. If the delivery tube <b>362</b> has a diameter that is substantially the same or slightly larger than a diameter of an aneurysm, then the stopper <b>400</b> may function as a back-up device for preventing excess fluid <b>350</b> from flowing into the artery or vein <b>402</b>. The stopper <b>400</b> is preferably made of a compressible or collapsible material, such as rubber or a foam-like material. However, other materials may also be used. The stopper <b>400</b> should have a shape and dimension such that it may substantially engage tissue around the neck of the aneurysm to substantially seal the aneurysm and prevent substantial leakage of fluid <b>350</b> into the artery or vein <b>402</b>.

The de-endothelialization fluid delivery device <b>360</b>(<b>4</b>) may optionally include a sheath <b>404</b> having a lumen <b>406</b>. As shown in <figref idrefs="DRAWINGS">FIG. 34B</figref>, the sheath <b>404</b> is capable of surrounding the distal end <b>364</b> of the delivery tube <b>362</b> such that the stopper <b>400</b> assumes a folded configuration when disposed within the lumen <b>406</b> of the sheath <b>404</b>. Depending on the geometry of the stopper <b>400</b>, the stopper <b>400</b> may also assume a compressed configuration when disposed within the lumen <b>406</b> of the sheath <b>404</b> (<figref idrefs="DRAWINGS">FIGS. 34C and 34D</figref>).

When using the de-endothelialization fluid delivery device <b>360</b>(<b>4</b>), the sheath <b>404</b> is first inserted into an artery or vein and advanced until the distal end of the sheath <b>404</b> is adjacent an aneurysm. The sheath <b>404</b> may be advanced over a guide wire or other rail, as is known in the art. The delivery tube <b>362</b> may be placed initially within the lumen <b>406</b> of the sheath <b>404</b> and the sheath <b>404</b> together with the delivery tube <b>362</b> may then be positioned adjacent the aneurysm. Alternatively, the delivery tube <b>362</b> may be inserted into the lumen <b>406</b> of the sheath <b>404</b> after the sheath <b>404</b> is desirably placed. The stopper <b>400</b> may assume a bent and/or compressed configuration when disposed within the lumen <b>406</b> of the sheath <b>404</b>.

The stopper <b>400</b> may be deployed, e.g., by retracting the sheath <b>404</b> relative to the tubular element <b>362</b>, or by advancing the delivery tube <b>362</b> relative to the sheath <b>404</b>. As shown in <figref idrefs="DRAWINGS">FIG. 34A</figref>, the stopper <b>400</b> may be deployed directly outside the neck of the aneurysm such that a distal side <b>412</b> of the stopper <b>400</b> engages with a vessel wall <b>413</b> directly outside the aneurysm so that the neck of the aneurysm is substantially sealed by the stopper <b>400</b>. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 34E</figref>, the stopper <b>400</b> can be deployed inside the neck of the aneurysm such that the proximal side <b>410</b> of the stopper <b>400</b> engages with the endothelium of the aneurysm.

The fluid <b>350</b> is then delivered to the aneurysm from the fluid supply <b>310</b>. After the fluid <b>350</b> contacts the endothelium of the aneurysm, the de-endothelialization property of the fluid <b>350</b> causes the endothelium of the aneurysm to be disrupted. The neck of the aneurysm is substantially sealed by the stopper <b>400</b> during the process such that fluid <b>350</b> may be drained or aspirated via a drainage port <b>390</b> without substantial leaking from the aneurysm into the artery or vein <b>402</b>. After a desired amount of the fluid <b>350</b> has been delivered and/or aspirated, the delivery tube <b>362</b> and the stopper <b>400</b> are then withdrawn back into the lumen <b>406</b> of the sheath <b>404</b>.

The shape of the stopper <b>400</b> should not be limited to the examples shown previously and that the stopper <b>400</b> may have other shapes. <figref idrefs="DRAWINGS">FIG. 34F</figref> shows a de-endothelialization fluid delivery device <b>360</b>(<b>5</b>) that includes a stopper <b>400</b> having an elliptical shape. When using the de-endothelialization fluid delivery device <b>360</b>(<b>5</b>), a portion of the stopper <b>400</b> may be inserted into the aneurysm until the stopper <b>400</b> bears against a surface <b>410</b> that defines the neck of the aneurysm. If desired, the distal end <b>364</b> of the delivery tube <b>362</b> may be advanced a relatively small increment to compress the stopper <b>400</b> within the neck of the aneurysm. This has the benefit of ensuring that the neck of the aneurysm is substantially sealed by the stopper <b>400</b>. The fluid <b>350</b> is then delivered into the aneurysm, as discussed previously. Fluid <b>350</b> delivered to the aneurysm may be aspirated or otherwise drained into a drainage port (now shown), the stopper <b>400</b> substantially preventing the fluid <b>350</b> from leaking from the aneurysm, as discussed previously.

<figref idrefs="DRAWINGS">FIG. 35</figref> shows a de-endothelialization fluid delivery device <b>414</b> in accordance with another embodiment of the present invention. The de-endothelialization fluid delivery device <b>414</b> includes an outer tubular element <b>415</b> and an inner tubular element <b>416</b> slidable within a lumen of the outer tubular element <b>415</b>. The outer tubular element <b>415</b>, which is preferably a micro-catheter or a sheath, may have a diameter that is the same or slightly larger than the neck of an aneurysm, as discussed previously with reference to <figref idrefs="DRAWINGS">FIG. 32</figref>. The proximal end of the inner tubular element <b>416</b> may be coupled to a source of de-endothelialization fluid (not shown).

When using the de-endothelialization fluid delivery device <b>414</b>, the distal tip of the outer tubular element <b>415</b> is first placed within the neck of an aneurysm or other body lumen, as shown in <figref idrefs="DRAWINGS">FIG. 35</figref>. The outer tubular element <b>415</b> may be placed and/or positioned using similar methods to those discussed previously, e.g., with reference to <figref idrefs="DRAWINGS">FIG. 32</figref>, or by conventionally known techniques. The inner tubular element <b>416</b> may be disposed within the lumen of the outer tubular element <b>415</b> and delivered together with the outer tubular element <b>415</b> to a target site. Alternatively, the inner tubular element <b>416</b> may be inserted into the lumen of the outer tubular element <b>415</b> after the outer tubular element <b>415</b> is desirably situated, and then advanced distally until it reaches the distal end of the outer tubular element <b>415</b>. Either or both of the outer and inner tubular elements may include one or more radio-opaque markers (not shown) at their respective distal ends for facilitating positioning the tubular elements.

When both the outer and inner tubular elements <b>415</b> and <b>416</b> are desirable positioned, de-endothelialization fluid is then delivered into the aneurysm or other body lumen via the inner tubular element <b>416</b>. Depending upon the size and geometry of the aneurysm or other body lumen, the inner tubular element <b>416</b> may be advanced and/or retracted relative to the outer tubular element <b>415</b> at various positions during and/or before delivering the de-endothelialization fluid. Excess de-endothelialization fluid may be aspirated or drained by the outer tubular element <b>415</b> during and/or after the delivery of the de-endothelialization fluid. After a desired amount of de-endothelialization has been delivered, the outer and inner tubular elements <b>415</b> and <b>416</b> are then withdrawn from the target site.

The de-endothelialization fluid delivery device <b>414</b> may further include a coil <b>417</b> secured to the distal end of the inner tubular element <b>416</b>, such as that shown in <figref idrefs="DRAWINGS">FIG. 36</figref>, to disperse the injected fluid within the aneurysm or other body lumen. The coil <b>417</b> is not limited to the linear shape shown in the illustrated embodiment, and may have other shapes as well. In particular, the coil <b>417</b> may have any of the secondary shapes discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 5-11</figref>. The coil <b>417</b> is preferably made from a radio-opaque material, such as platinum. However, other materials such as stainless steel, aluminum, and/or plastic, may also be suitable for constructing the coil <b>417</b>. Generally, any of the materials discussed previously with reference to the core member <b>12</b> may also be used. The length of the coil <b>417</b> is preferably from about two millimeters (2 mm) to about three hundred millimeters (300 mm). The coil <b>417</b> may also have other lengths, depending on the particular application. The spacing between the windings of the coil <b>417</b> may vary. Generally, smaller spacing between the windings may better disperse the de-endothelialization fluid.

In the illustrated embodiment, the coil <b>417</b> is secured to the distal end of the inner tubular element <b>416</b> by an epoxy <b>418</b>. Other suitable adhesives may also be used. As shown in <figref idrefs="DRAWINGS">FIG. 36</figref>, the proximal end of the coil <b>417</b> fits around the distal end of the inner tubular element <b>416</b>. Alternatively, the proximal tip of the coil <b>417</b> may abut and be secured to the distal tip of the inner tubular element <b>416</b>, as shown in <figref idrefs="DRAWINGS">FIG. 37</figref>. The de-endothelialization fluid delivery device <b>414</b> may further include an atraumatic tip <b>419</b> secured to the distal end of the coil <b>417</b>.

When using the de-endothelialization fluid delivery device <b>414</b> of <figref idrefs="DRAWINGS">FIG. 36</figref> in an aneurysm, the distal end of the outer tubular element <b>415</b> is first placed within the neck of then aneurysm, as discussed previously, e.g., with reference to <figref idrefs="DRAWINGS">FIG. 35</figref>. The inner tubular element <b>416</b> is then advanced within the lumen of the outer tubular element <b>415</b> until the coil <b>417</b> extends at least partially beyond the distal end of the outer tubular element <b>415</b> and into the aneurysm. If the coil <b>417</b> has a secondary shape or configuration, it may attempt to return towards the secondary shape as it is deployed from the lumen of the outer tubular element <b>415</b>. De-endothelialization fluid may then be delivered via the inner tubular element <b>416</b> into the lumen of the coil <b>417</b>, where it may escape through spaces between the windings of the coil <b>417</b>. The windings of the coil <b>417</b> may disperse the de-endothelialization fluid within the aneurysm. De-endothelialization fluid may then be aspirated or drained by the outer tubular element <b>415</b>. When a desired amount of the de-endothelialization fluid has been delivered and/or aspirated, the outer and inner tubular elements <b>415</b> and <b>416</b> may then be withdrawn from the treatment site.

It should be understood by those skilled in the art that the outer tubular element <b>415</b> discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 35-37</figref> is primarily used to aspirate excess delivered de-endothelialization fluid, and that, optionally, it may be eliminated (or if provided, it may not necessarily be placed within the neck of the aneurysm) if the de-endothelialization fluid may be mixed safely with blood. In this case, the de-endothelialization fluid may leak out of the sac of the aneurysm without being aspirated or drained by the outer tubular element <b>415</b>.

<figref idrefs="DRAWINGS">FIG. 38A</figref> shows a de-endothelialization fluid delivery device <b>420</b> that includes a balloon <b>422</b> having a lumen <b>424</b> (shown in <figref idrefs="DRAWINGS">FIG. 38B</figref>), a delivery tube <b>426</b>, and a sheath <b>428</b>. The sheath <b>428</b> preferably has a diameter or cross-sectional dimension that is the same or slightly larger than that of a neck of an aneurysm so that it can be used to aspirate de-endothelialization fluid from the aneurysm, as discussed previously with reference to the outer tubular element <b>415</b> in <figref idrefs="DRAWINGS">FIGS. 35-37</figref>. The balloon <b>422</b> is preferably made of a compliant material, such as silicone, rubber, low density polyethylene, high density polyethylene, polypropylene, polybutene, interpolymers or mixtures of these polymers, so that when it is inflated, it may conform to the shape of an aneurysm. In general, any of the materials discussed previously with reference to the balloon <b>170</b> of <figref idrefs="DRAWINGS">FIG. 25A</figref> is also applicable for constructing the balloon <b>422</b>. The balloon <b>422</b> is not limited to the shape shown in the illustrated embodiment, and may have other shapes as well.

The delivery tube <b>426</b> includes a distal end <b>430</b>, a proximal end <b>432</b> (not shown), and a lumen <b>434</b> (<figref idrefs="DRAWINGS">FIG. 38B</figref>) extending between the distal end <b>430</b> and the proximal end <b>432</b>. The distal end <b>430</b> of the delivery tube <b>426</b> is coupled to the balloon <b>422</b> such that the lumen <b>424</b> of the balloon <b>422</b> communicates with the lumen <b>434</b> of the delivery tube <b>426</b>. The balloon <b>422</b> includes one or more openings <b>436</b> that communicate with the lumen <b>424</b> of the balloon <b>422</b>. The opening <b>436</b> has a size such that, when the balloon <b>422</b> is inflated by fluid, the opening <b>436</b> may expand sufficiently to allow fluid to exit the balloon <b>422</b>.

As shown in <figref idrefs="DRAWINGS">FIG. 39A</figref>, the de-endothelialization device <b>420</b> may further include one or more drainage ports <b>440</b> located at a surface of the balloon <b>422</b>, through which fluid <b>350</b> may be aspirated and delivered back to a proximal end (not shown) of the delivery tube <b>426</b> via a drainage lumen <b>442</b>. <figref idrefs="DRAWINGS">FIG. 39B</figref> is a cross sectional view of the delivery tube <b>426</b>, showing the drainage lumen <b>442</b> inside a wall of the delivery tube <b>426</b>. <figref idrefs="DRAWINGS">FIGS. 40A and 40B</figref> show a variation of the de-endothelialization fluid delivery device <b>420</b> in which the drainage lumen <b>442</b> is a separate drainage tube <b>448</b> surrounded by the delivery tube <b>428</b>. It should be noted that the location and number of drainage ports <b>440</b> and the shape of the balloon may vary, and that they should not be limited to the examples shown in the illustrated embodiments.

<figref idrefs="DRAWINGS">FIG. 41</figref> shows another variation of the de-endothelialization fluid delivery device <b>420</b> that includes a sealing member or stopper <b>450</b> secured to the balloon <b>422</b>. Although the illustrated embodiment shows that the stopper <b>450</b> extends above the surface of the balloon <b>422</b>, the stopper <b>450</b> may also be constructed such that it is flush with the surface of the balloon <b>422</b>. The stopper <b>450</b> may have a variety of shapes, and is not limited to the planar configuration shown in the illustrated embodiment. Furthermore, the stopper <b>450</b> may be secured to the distal end of the delivery tube <b>428</b> (not shown, see <figref idrefs="DRAWINGS">FIG. 38A</figref>) instead of to the balloon <b>422</b> so long as the stopper <b>450</b> is capable of sealing the neck of the aneurysm to prevent fluid <b>350</b> from leaving the aneurysm. In general, any of the materials discussed previously with reference to the stopper <b>400</b> may be used for the stopper <b>450</b>.

When using the de-endothelialization fluid delivery device <b>420</b>, the balloon <b>422</b> is inflated within the aneurysm by delivering fluid <b>350</b> via the delivery tube <b>426</b> into the lumen <b>424</b> of the balloon <b>422</b>. When the balloon <b>422</b> is inflated to a certain size, the fluid <b>350</b> exits through the opening(s) <b>436</b> of the balloon <b>422</b> due to internal pressure within the balloon <b>422</b> and/or the size of the opening(s) <b>436</b> increasing as the balloon <b>422</b> expands. The fluid <b>350</b> then contacts the endothelium of the aneurysm, thereby disrupting the endothelium. If the de-endothelialization fluid delivery device <b>420</b> includes a drainage port <b>440</b>, it may be used to aspirate fluid <b>350</b> from within the aneurysm. Alternatively, if the de-endothelialization fluid delivery device <b>420</b> includes a stopper <b>450</b>, the stopper <b>450</b> may be used to absorb fluid <b>350</b> within the aneurysm. When the de-endothelialization process is complete, the balloon <b>422</b> may be deflated and removed from the aneurysm.

<figref idrefs="DRAWINGS">FIG. 42A</figref> shows another variation of the de-endothelialization fluid delivery device <b>420</b> that includes a separate delivery lumen <b>460</b> for delivering fluid to an aneurysm. In this case, the delivery tube <b>426</b> (not shown, see <figref idrefs="DRAWINGS">FIG. 38A</figref>) may be used to deliver an inflation fluid, such as water, saline, blood, and/or de-endothelialization fluid <b>350</b> to the lumen <b>424</b> of the balloon <b>422</b> to inflate the balloon <b>422</b>. After the balloon <b>422</b> has been inflated to a desired size, the de-endothelialization fluid may be delivered via the delivery lumen <b>460</b> to the aneurysm. <figref idrefs="DRAWINGS">FIG. 42A</figref> shows that the delivery lumen <b>460</b> is formed within a wall of the delivery tube <b>428</b>. Alternatively, as shown in <figref idrefs="DRAWINGS">FIG. 42B</figref>, a separate tube <b>462</b> may provide the delivery lumen <b>460</b>. The tube <b>462</b> is coaxially surrounded by the delivery tube <b>428</b>. In either case, the de-endothelialization device <b>420</b> may optionally include a drainage port <b>440</b> or a stopper <b>450</b> as discussed previously.

Optionally, any of the de-endothelialization fluid delivery devices described previously with reference to <figref idrefs="DRAWINGS">FIGS. 31-42B</figref> may be used with a perfusion balloon <b>600</b>, such as that shown in <figref idrefs="DRAWINGS">FIG. 43A</figref>. The perfusion balloon <b>600</b> has a lumen <b>602</b>, and is coupled to an inflation tube <b>604</b> such that the lumen <b>602</b> of the perfusion balloon <b>600</b> is in fluid communication with a lumen of the inflation tube <b>604</b>. The perfusion balloon <b>600</b> has a shape such that when it is inflated, it defines an opening <b>608</b> for allowing blood to flow through the perfusion balloon <b>600</b>. The perfusion balloon <b>600</b> is preferably made of an elastic material, such as a polymer. In general, any of the materials discussed previously with reference to the balloon <b>170</b> of <figref idrefs="DRAWINGS">FIG. 25A</figref> may also be used. However, other materials may also be used.

Before using the perfusion balloon <b>600</b>, a de-endothelialization fluid delivery device <b>609</b> is first placed adjacent or within an aneurysm. The de-endothelialization fluid delivery device <b>609</b> is representative of any of the de-endothelialization fluid delivery devices described previously with reference to <figref idrefs="DRAWINGS">FIGS. 31-42B</figref>. When using the perfusion balloon <b>600</b>, the perfusion balloon <b>600</b> is delivered to a site where the aneurysm is located. A sheath <b>610</b> may be used to deliver the perfusion balloon <b>600</b>. If the de-endothelialization device <b>609</b> includes a sheath, the sheath of the de-endothelialization device may also be used instead to deliver the perfusion balloon <b>600</b>. The perfusion balloon <b>600</b> is collapsed and assumes a low profile when disposed within the lumen of the sheath.

Once the sheath <b>610</b> is adjacent the aneurysm, the perfusion balloon <b>600</b> is deployed from the distal end of the sheath, either by distally advancing the perfusion balloon <b>600</b> relative to the distal end of the sheath <b>610</b>, or by retracting the sheath <b>610</b> relative to the perfusion balloon <b>600</b>. An inflation fluid, such as saline, water, blood, or gas is then delivered by the inflation tube <b>604</b> to within the lumen <b>602</b> of the perfusion balloon <b>600</b>, thereby expanding the perfusion balloon <b>600</b> until a surface <b>612</b> of the perfusion balloon <b>600</b> engages the vessel wall <b>614</b>. As shown in <figref idrefs="DRAWINGS">FIG. 43A</figref>, when the perfusion balloon <b>600</b> is inflated, it forms a barrier substantially sealing the neck of the aneurysm, thereby reducing the chance that fluid <b>350</b> delivered into the aneurysm may escape into the vessel or artery.

<figref idrefs="DRAWINGS">FIG. 43B</figref> shows a variation of the perfusion balloon <b>600</b> that includes a slot <b>620</b> in which a portion of the de-endothelialization fluid delivery device <b>609</b> may be placed. The slot <b>620</b> preferably has a depth <b>622</b> that is substantially the same as a diameter of the de-endothelialization fluid delivery device <b>609</b>. This may allow the de-endothelialization fluid delivery device <b>609</b> to form a substantially continuous surface with the perfusion balloon <b>600</b> to better engage the wall <b>614</b> of the vessel or artery, as shown in <figref idrefs="DRAWINGS">FIG. 43C</figref>.

<figref idrefs="DRAWINGS">FIG. 44A</figref> shows a de-endothelialization fluid delivery device <b>640</b> that includes a balloon <b>642</b> and a triple-lumen catheter <b>644</b>. The balloon <b>642</b> is coupled to a distal portion <b>646</b> of the triple-lumen catheter <b>644</b>. As shown in <figref idrefs="DRAWINGS">FIG. 44B</figref>, the triple-lumen catheter <b>644</b> includes a first lumen <b>648</b> that communicates with a lumen <b>650</b> of the balloon <b>642</b>, a second lumen <b>652</b> for delivering de-endothelialization fluid <b>350</b> to an aneurysm, and a third lumen <b>654</b> for aspirating fluid <b>350</b> from the aneurysm. It should be noted that the association of specific lumens with respective purposes is merely a matter of design choice, and that any of the lumens <b>648</b>, <b>652</b>, and <b>654</b> may be used for inflating the balloon <b>642</b>, delivering fluid <b>350</b>, and draining fluid. The balloon <b>642</b> includes one or more openings <b>658</b> communicating with the second lumen <b>652</b> of the triple-lumen catheter <b>644</b>, and one or more drainage ports <b>660</b> communicating with the third lumen <b>654</b> of the triple-lumen catheter <b>644</b>. The balloon <b>642</b> preferably has a tubular shape, e.g., similar to the perfusion balloon <b>600</b> discussed previously, such that blood may continue to flow through the vein or artery while the fluid <b>350</b> is being delivered to the aneurysm. The de-endothelialization fluid delivery device <b>640</b> may further include a sheath <b>661</b>.

The triple-lumen catheter <b>644</b> is not necessarily limited to the configuration described previously. <figref idrefs="DRAWINGS">FIG. 44C</figref> shows a variation of the triple-lumen catheter <b>644</b> that includes a first tube <b>662</b> defining the first lumen <b>648</b>, a second tube <b>664</b> defining a second lumen <b>652</b>, and a third tube <b>666</b> defining a third lumen <b>654</b>. The first tube <b>662</b> coaxially surrounds the second tube <b>664</b> and the third tube <b>666</b>. <figref idrefs="DRAWINGS">FIG. 44D</figref> shows another variation of the triple-lumen catheter <b>644</b> in which the first tube <b>662</b> surrounds the second tube <b>664</b>, and the second tube <b>664</b>, in turn, surrounds the third tube <b>666</b>.

When using the de-endothelialization fluid delivery device <b>640</b>, the balloon <b>642</b> is first placed adjacent to a neck of the aneurysm. The balloon <b>642</b> may be delivered using a sheath <b>661</b> and/or a guide wire, as is known in the art. For example, the sheath <b>661</b> may be advanced over a guide wire (not shown) through a vasculature until the distal end of the sheath <b>661</b> is adjacent to the neck of the aneurysm. The balloon <b>642</b> coupled to the triple-lumen catheter <b>644</b> may then be deployed from the lumen of the sheath <b>661</b>, e.g., by advancing the balloon <b>642</b> into the lumen from the proximal end of the sheath <b>661</b> until it emerges at the distal end of the sheath <b>661</b>.

Before and/or after the balloon <b>642</b> exits the lumen of the sheath <b>661</b>, if required, the position and/or the orientation of the balloon may be adjusted by advancing, retracting, and/or rotating the proximal end of the triple-lumen catheter <b>644</b>, until the openings <b>658</b> and <b>660</b> of the balloon <b>642</b> face the opening of the aneurysm. The balloon <b>642</b> is then inflated by a media, such as saline, a gas, or other fluid. The balloon <b>642</b> substantially closes the neck opening of the aneurysm while allowing blood to flow through the vein or artery. Next, de-endothelialization fluid <b>350</b> may be delivered through the second lumen <b>652</b> of the triple-lumen catheter <b>644</b> into the aneurysm. If the de-endothelialization fluid delivery device <b>640</b> includes a drainage port <b>660</b>, fluid <b>350</b> may be aspirated from the aneurysm via then port <b>660</b>. After a desired amount of the fluid <b>350</b> has been delivered, the balloon <b>642</b> is then deflated and withdrawn into the lumen of the sheath <b>661</b>.

<figref idrefs="DRAWINGS">FIG. 45</figref> shows another de-endothelialization fluid delivery device <b>690</b> that includes an applicator <b>692</b>, a tube <b>694</b>, and a sheath <b>695</b>. The applicator is coupled to a distal end <b>696</b> of the tube <b>694</b>, and is capable of being compressed into a low profile when disposed within the lumen of the sheath <b>695</b> (<figref idrefs="DRAWINGS">FIG. 46</figref>). The applicator <b>692</b> is made of a porous and/or absorptive material, e.g., similar to a sponge. The tube <b>694</b> also has a proximal end <b>698</b> that is coupled to the fluid source <b>370</b>. When using the de-endothelialization device <b>690</b>, the applicator <b>692</b> is first deployed into an aneurysm. De-endothelialization fluid <b>350</b> is then delivered via the tube <b>694</b> to the applicator <b>692</b>. Alternatively, the applicator <b>692</b> may also be deployed into the aneurysm after the fluid <b>350</b> is delivered to the applicator <b>692</b>. The applicator <b>692</b> controls the amount of fluid <b>350</b> that may be delivered to the aneurysm, thereby reducing the risk of having excess fluid <b>350</b> flowing from the aneurysm to an artery or vessel. It should be noted that applicator <b>692</b> may have other shapes and/or that other types of applicators known in the art may also be used.

Turning to <figref idrefs="DRAWINGS">FIGS. 52A-52E</figref>, a system <b>810</b> is shown for treating an aneurysm <b>90</b> extending from a body lumen, such as a cerebral artery or other blood vessel <b>92</b>. Generally, the system <b>810</b> includes an outer tubular member <b>812</b> including a proximal end (not shown), a distal end <b>814</b> having a size and shape for insertion into the aneurysm <b>90</b>, and a lumen <b>816</b> extending between the proximal end and distal end <b>814</b>. The system <b>10</b> also includes an inner tubular member <b>822</b> disposed within the outer tubular member <b>812</b> that also includes a lumen <b>826</b>. The inner tubular member <b>822</b> may be slidable relative to the outer tubular member <b>812</b>, e.g., to retract or expose a distal end <b>824</b> of the inner tubular member <b>822</b>, as will be appreciated by those skilled in the art.

The inner tubular member <b>822</b> is substantially smaller than the outer tubular member <b>812</b> such that the lumen <b>816</b> between the inner and outer tubular members <b>822</b>, <b>812</b> has a generally annular cross-section. The lumen <b>826</b> within the inner tubular member <b>822</b> may be coupled to a source of fluid (not shown), thereby providing an infusion lumen, while the annular lumen <b>816</b> may be coupled to a source of vacuum (also not shown), thereby providing an aspiration lumen. Alternatively, the functions of these lumens <b>816</b>, <b>826</b> may be reversed or they may coupled to other components, as will be appreciated by those skilled in the art.

Turning to <figref idrefs="DRAWINGS">FIG. 53</figref>, a dual syringe apparatus <b>850</b> is shown that may be coupled to the inner and/or outer tubular members <b>822</b>, <b>812</b> shown in <figref idrefs="DRAWINGS">FIGS. 52A-52E</figref>, e.g., by tubing <b>818</b>, <b>828</b>. Generally, the apparatus <b>850</b> includes first and second syringe barrels <b>852</b>, <b>862</b> including first and second chambers <b>854</b>, <b>864</b> and first and second pistons <b>856</b>, <b>866</b>, respectively. The barrels <b>852</b>, <b>862</b> may have similar cross-sections or different cross-sections, depending upon whether the delivery and aspiration should be the same or different from one another. The first and second pistons <b>856</b>, <b>866</b> are movable within the first and second chambers, respectively, for delivering fluid and/or for aspirating fluid, as explained further below. In addition, the first barrel <b>852</b> includes an outlet port <b>858</b> and the second barrel <b>862</b> has an inlet port <b>868</b> to which tubing <b>828</b>, <b>818</b> may be connected using conventional methods, e.g., luer lock connectors and the like (not shown).

The system <b>850</b> also includes an actuator <b>870</b> for moving the first piston <b>856</b>, e.g., to deliver fluid within the first chamber <b>854</b>, and/or for moving the second piston <b>866</b>, e.g., to aspirate fluid into the second chamber <b>864</b>. In the preferred embodiment shown, the actuator <b>870</b> includes a motor <b>872</b> with an output shaft <b>874</b> that is coupled to shafts <b>876</b>, <b>886</b>, e.g., via sprockets or wheels <b>878</b>, <b>888</b>. Preferably, the wheels <b>878</b>, <b>888</b> are coupled to one another such that, when the motor <b>872</b> is operated, the output shaft <b>874</b> simultaneously rotates the wheels <b>878</b>, <b>888</b>, thereby simultaneously advancing and retracting the pistons <b>856</b>, <b>866</b>, respectively. It will be appreciated that other actuators may also be provided that may be operated manually and/or automatically, instead of the motor and shaft arrangement shown in <figref idrefs="DRAWINGS">FIG. 53</figref>. In addition, the volumetric rates of fluid delivery and fluid aspiration need not be the same.

It will be appreciated that other fluid moving elements may be provided in addition to or instead of the dual syringes described above. For example a fluid delivery pump and as aspiration pump may be coupled to the delivery and aspiration lumens and to an actuator for simultaneously delivering and aspirating fluid, as described elsewhere herein.

Returning to <figref idrefs="DRAWINGS">FIGS. 52A-52E</figref>, optionally, the system <b>810</b> may include an occlusion member <b>830</b> for substantially sealing the aneurysm <b>90</b> from the vessel <b>92</b>. In the embodiment shown, the occlusion member <b>830</b> includes an expandable member <b>832</b> carried on a distal end <b>834</b> of an elongate member <b>836</b>. In a preferred embodiment, the expandable member <b>832</b> is a compliant, nonporous balloon and the elongate member <b>836</b> is a catheter or micro-catheter including an inflation lumen for infusing fluid into and/or aspirating fluid from the balloon. Alternatively, a mechanically expandable member (not shown) or other sealing member may be provided. In a further alternative, an expandable member (not shown) may be provided proximate to the distal end of the outer tubular member <b>812</b>, rather than on a separate member.

In other alternatives, similar to the embodiment described above, the inner member may be eliminated, and the outer tubular member may include two lumens, one for infusion and one for aspiration (not shown). The lumens may be arranged coaxially, side-by-side, or in any other configuration. The distal end of the outer tubular member may include one or more ports spaced apart from one another in a desired arrangement, with one or more ports communicating with respective lumens.

In yet another alternative, the expandable member may include one or more ports, and the elongate member may include one or more additional lumens communicating with respective ports, e.g., for infusing or aspirating fluid, similar to the embodiments described above with reference to <figref idrefs="DRAWINGS">FIG. 44A</figref>. This may allow the inner tubular member to be eliminated, while only requiring the outer tubular member to include one lumen, or may even allow both tubular members to be eliminated.

Returning to <figref idrefs="DRAWINGS">FIGS. 52A-52E</figref>, a method is shown for treating a malformation, such as an aneurysm <b>90</b>, extending from a body lumen, such as a blood vessel <b>92</b>. Initially, the outer tubular member <b>812</b> may be introduced into the patient's vasculature, e.g., from a percutaneous entry site, and advanced over a guidewire (not shown) until the distal end <b>814</b> is located within the aneurysm <b>90</b>. The outer tubular member <b>812</b> may include a substantially rounded and/or atraumatic tip to facilitate advancing the outer tubular member <b>812</b> through tortuous anatomy, as is well known in the art.

The occlusion member <b>830</b> may be advanced into the vessel <b>92</b> until the expandable member <b>832</b> is disposed adjacent the aneurysm <b>90</b>. The occlusion member <b>830</b> may be delivered within a catheter, sheath, or other device, e.g., to protect the expandable member <b>832</b> and/or the patient. Once the expandable member <b>832</b> is properly positioned, it may be expanded to substantially seal the aneurysm <b>90</b> from the vessel <b>92</b>, as shown in <figref idrefs="DRAWINGS">FIG. 52A</figref>. Preferably, the expandable member <b>832</b> substantially engages the outer tubular member <b>812</b>, e.g., to enhance the seal against the vessel <b>92</b> and/or to prevent axial movement of the outer tubular member <b>812</b> relative to the aneurysm <b>90</b>.

Material, such as blood, other fluid, and/or particulate, may be aspirated from aneurysm, e.g., to substantially clear the interior of the aneurysm <b>90</b>. Preferably, as shown in <figref idrefs="DRAWINGS">FIG. 52B</figref>, heparinized saline or other isotonic solution with or without a contrast agent is delivered, e.g., via the lumen <b>826</b> within the inner tubular member <b>822</b>, into the aneurysm <b>90</b> to facilitate clearing the interior of the aneurysm <b>90</b>. More preferably, the saline or other solution is infused into the aneurysm <b>90</b> substantially simultaneously with aspirating excess fluid, e.g., saline, solution, blood, and/or loose particulate, from the aneurysm <b>90</b>, e.g., using an actuator such as the system <b>850</b> shown in <figref idrefs="DRAWINGS">FIG. 53</figref>.

Because of the occlusion member <b>830</b>, the fluid being infused into and/or aspirated from the aneurysm <b>90</b> without leaking substantially into the vessel <b>92</b>. In alternative embodiment, the occlusion member <b>830</b> may not be expanded to substantially seal the aneurysm <b>90</b> during the infusion and/or aspiration of fluid to clear the aneurysm, e.g., if the fluid is substantially harmless if it travels downstream in the vessel <b>92</b>.

Turning to <figref idrefs="DRAWINGS">FIG. 52C</figref>, a therapeutic fluid may then be delivered into the aneurysm <b>90</b>. The therapeutic fluid may be intended to cause a variety of reactions within the aneurysm <b>90</b>, e.g., cellular lysis, disruption of cellular adhesions, and/or disruption of cellular function. For example, the therapeutic fluid may include distilled water, a hypo-osmotic solution, a hyper-osmotic solution, a detergent, a membrane disruptive polymer solution, and/or a membrane disruptive protein solution capable of causing cellular lysis within the wall of the aneurysm <b>90</b>.

In addition or alternatively, the therapeutic agent may include a solution capable of disrupting intercellular adhesions, such as proteolytic enzymes (e.g., trypsin), or other agents that disrupt adhesive connections between cells. In a further alternative, the therapeutic fluid may include a solution capable of disrupting or ceasing one or more cellular functions, such as ethanol, a chemotherapeutic agent, a cytostatic agent, and/or a cytotoxic agent. Optionally, the therapeutic agent may include x-ray contrast, e.g., to identify when at least some therapeutic agent remains within the aneurysm <b>90</b>.

As shown in <figref idrefs="DRAWINGS">FIG. 52D</figref>, once the therapeutic agent has had an opportunity to act within the aneurysm, the therapeutic fluid may be aspirated from the aneurysm. Preferably, fluid, such as saline or other isotonic solution with or without a contrast agent, is infused into the aneurysm <b>90</b> substantially simultaneously with aspirating excess fluid including the therapeutic fluid from the aneurysm. Alternatively, sufficient vacuum may be maintained such that the expandable member <b>852</b> may be at least partially collapsed, thereby allowing fluid from the vessel <b>92</b> to enter the aneurysm <b>90</b> and fill the void as fluid is aspirated.

Finally, as shown in <figref idrefs="DRAWINGS">FIG. 52E</figref>, once the therapeutic agent has been substantially removed from the aneurysm <b>90</b>, the expandable member <b>832</b> may be collapsed, e.g., by aspirating the fluid infused into the expandable member <b>832</b>. The outer tubular member <b>812</b>, inner tubular member <b>822</b>, and/or the occlusion member <b>850</b> may then be removed from the vessel <b>92</b> and from the patient's body, e.g., using conventional procedures.

Turning to <figref idrefs="DRAWINGS">FIG. 54</figref>, a similar method is shown for treating an arterio-venous malformation <b>94</b> that extends between″an artery <b>96</b> and a vein <b>98</b>. Unlike the previous embodiment, separate balloon catheters <b>860</b>, <b>870</b> may be introduced into the artery <b>96</b> and the vein <b>98</b> using conventional methods. Once positioned as desired, balloons <b>862</b>, <b>872</b> on the catheters <b>860</b>, <b>870</b> may be expanded to engage the artery <b>96</b> and vein <b>98</b>, respectively, thereby substantially isolating the malformation <b>94</b> from the artery <b>96</b> and vein <b>98</b>.

Fluid within the malformation <b>94</b> may be aspirated, e.g., using the catheter <b>870</b> either alone or in conjunction with infusion of saline and the like, e.g., using the catheter <b>860</b>. Thus, one catheter may be used for infusion while the other is used for aspiration. Optionally, the system <b>850</b> shown in <figref idrefs="DRAWINGS">FIG. 53</figref> or other actuator may be used to infuse and aspirate substantially simultaneously, as described above. Once the malformation is sufficiently cleared, a therapeutic agent, similar to those described above, may be introduced, e.g., from one or both catheters. Optionally, excess fluid may be aspirated from the malformation <b>94</b> either during or after the therapeutic agent is introduced, similar to the method described above. Once the therapeutic agent has remained within the malformation <b>94</b> for sufficient time, the therapeutic agent may be aspirated, e.g., in conjunction with fluid infusion, similar to the previous embodiments. The balloons <b>862</b>, <b>872</b> may be collapsed and the catheter <b>860</b>, <b>870</b> removed from the artery <b>96</b> and vein <b>98</b>.

Alternatively, a similar method may be used for introducing a de-endothelialization agent into other blood vessels. For example, a balloon catheter, similar to those described above may be introduced into a blood vessel adjacent a target treatment site within a blood vessel, e.g., from a retrograde approach (not shown). A balloon or other occlusion member may be expanded to engage the wall of the vessel, and a therapeutic fluid may be introduced via the catheter into the target side, e.g., distal to or upstream from the balloon. The fluid may at least partially de-endothelialize the vessel wall, e.g., to cause fibrous growth that may strengthen the vessel wall and/or may occlude the vessel at the treatment site.

B. Delivery of De-Endothelialization Fluid Using an Implantable Device

De-endothelialization fluid <b>350</b> may also be delivered to an aneurysm or other body lumen using an implantable device, such as a vaso-occlusive device. <figref idrefs="DRAWINGS">FIG. 47</figref> shows a de-endothelialization device <b>700</b> that may be used to deliver a de-endothelialization fluid or composition to an aneurysm or other body lumen. The de-endothelialization device <b>700</b> includes a core member <b>702</b> and a fiber <b>704</b> secured to the core member <b>702</b>. The fiber <b>704</b> is capable of absorbing and/or retaining fluid, e.g., by capillary action. Alternatively, the fiber <b>704</b> may carry de-endothelialization agents that are chemically or physically attached to the fiber <b>704</b>.

<figref idrefs="DRAWINGS">FIG. 48</figref> shows a variation of the de-endothelialization device <b>700</b> in which the fiber <b>704</b> is substantially longitudinally oriented and is secured to the core member <b>702</b> at one or more locations <b>706</b> along a length of the core member <b>702</b>. <figref idrefs="DRAWINGS">FIG. 49</figref> shows another variation of the de-endothelialization device <b>700</b> in which one or more fibers <b>704</b> are arranged into a mesh that is secured to the core member <b>702</b>. The fiber(s) <b>704</b> may be arranged in a variety of patterns and are not limited to those shown previously.

The core member <b>702</b> may be made from a variety of materials. In general, any of the materials discussed previously with reference to the core member <b>12</b> of <figref idrefs="DRAWINGS">FIG. 1</figref> is also applicable the core member <b>702</b> of the de-endothelialization device <b>700</b>. The core member <b>702</b> may also assume a variety of shapes. Any of the shapes discussed previously with reference to <figref idrefs="DRAWINGS">FIGS. 1-11</figref> may also be used.

When using the de-endothelialization device <b>700</b>, the de-endothelialization device <b>700</b> may be dipped into a de-endothelialization fluid, which may be absorbed and/or otherwise retained by the fiber <b>704</b> of the de-endothelialization device <b>700</b>. The de-endothelialization device <b>700</b> may then be delivered to an aneurysm or other body lumen using any of the methods described previously with reference to <figref idrefs="DRAWINGS">FIGS. 12-15</figref>, or any conventionally known method. After the de-endothelialization device <b>700</b> contacts the endothelium of the aneurysm or other body lumen, the fluid <b>350</b> then causes the endothelium to be disrupted, as discussed previously.

It should be noted that instead of using the de-endothelialization device <b>700</b> described previously, a similar procedure may be completed using any implantable object, such as a vaso-occlusive device. In particular, a vaso-occlusive device may be dipped into de-endothelialization fluid, which may then adhere to a surface of the vaso-occlusive device by surface adhesion. The vaso-occlusive device, carrying the fluid, may then be delivered to an aneurysm or other body lumen.

<figref idrefs="DRAWINGS">FIG. 50</figref> shows another de-endothelialization device <b>720</b> that includes a core member <b>722</b> and a coating <b>724</b> secured to the core member <b>722</b>. The coating <b>724</b> is preferably secured to the core member <b>722</b> during manufacturing. However, the coating <b>724</b> may also be applied on the core member <b>722</b> by a user immediately before a procedure. The coating <b>724</b> may be applied to the core member <b>722</b>, for example, by dipping the core member <b>722</b> into a solution. The coating <b>724</b> may contain similar de-endothelializing ingredients, such as a cytotoxic agent, as that of de-endothelialization fluids described above. When the de-endothelialization device <b>720</b> is placed within an aneurysm, a body temperature and/or a chemical reaction may be used to degrade or dissolve the coating <b>724</b> to release the de-endothelializing ingredients. When the endothelium of the aneurysm or other body lumen is contacted by the de-endothelializing ingredients, the endothelium is then disrupted.

De-endothelialization fluid <b>350</b> may also be delivered via a hydrogel coating. <figref idrefs="DRAWINGS">FIG. 51</figref> shows a de-endothelialization device <b>730</b> having a hydrogel coating <b>732</b> coupled to a core member <b>734</b>. The hydrogel coating <b>732</b> is capable of absorbing a desired amount of de-endothelialization fluid. Examples of hydrogels include gels formed from polysaccharides, mucopolysaccharides, polyaminoacids, proteins that support cell growth and healing, polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, carboxy alkyl celluloses, partially oxidized cellulose, polymers and oligomers of glycolide and lactide, polylactic acid, polyesters of .alpha.-hydroxy acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and combinations thereof. Other examples of hydrogels may also include gels formed from hyaluronic acid, dextran, heparin sulfate, chondroitin sulfate, heparin, agar, starch, alginate, fibronectin, gelatin, collagen, fibrin, pectins, albumin, ovalbumin, collagen-hydroxyethyl-methacrylate (HEMA); diacrylates, oligoacrylates, methacrylates, dimethacrylates, oligomethoacrylates, PEG-oligoglycolylacrylates, carboxymethyl cellulose, polyesters of lactic acid, polyesters of glycolic acid, poly(.alpha.-hydroxy) acids including polyglycolic acid, poly-DL-lactic, poly-L-lactic acid, and terpolymers of DL-lactide and glycolide, .epsilon.-caprolactone, .epsilon.-caprolactone copolymerized with polyesters, poly(.epsilon.-caprolactone), poly(.delta.-valerolactone), poly(gamma-butyrolactone), and combinations thereof. When using the de-endothelialization device <b>730</b>, the de-endothelialization device <b>730</b> is first dipped into de-endothelialization fluid. Due to the absorptive characteristic of the hydrogel coating <b>732</b>, the hydrogel coating <b>732</b> absorbs the fluid and retains the fluid within the coating <b>732</b>.

The endothelialization device <b>730</b> may then be delivered to an aneurysm or other body lumen using any of the methods discussed previously. Once situated inside the sac of the aneurysm or at the site of another body lumen, the fluid may diffuse from the hydrogel coating <b>732</b> and contact the endothelium of the aneurysm or other body lumen to disrupt the endothelium.

Although several embodiments and methods of de-endothelializing an aneurysm or other body lumen have been described, it should be noted that one or more of the above described embodiments may be combined with another. For example, the de-endothelialization device <b>10</b> described with reference to <figref idrefs="DRAWINGS">FIGS. 1-11</figref> may also be heated and/or dipped into de-endothelialization fluid to enhance its de-endothelialization properties. Also, the de-endothelialization device <b>300</b> described previously with reference to <figref idrefs="DRAWINGS">FIG. 30</figref> can also include an abrasive element <b>14</b>, such as that shown in <figref idrefs="DRAWINGS">FIG. 1</figref>, to enhance its de-endothelialization property. Combination of other embodiments described previously may also be used.

Furthermore, although the embodiments have been discussed with reference to treating aneurysms, the scope of the invention should not be so limited. For example, any of the above described embodiments may also be used to de-endothelialize vascular tissue for treating arteriovenous malformations (AVMs), arteriovenous fistulas (AVFs), or other vascular conditions. Other bodily tissues may also be de-endothelialized for treatment of various medical conditions, such as tumors, using any of the above discussed devices and/or methods.

Thus, although several preferred embodiments have been shown and described, it would be apparent to those skilled in the art that many changes and modifications may be made thereto without departing from the scope of the invention, which is defined by the following claims and their equivalents.